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Sample records for bcg live tice

  1. Size characterization of Mycobacterium bovis BCG (Bacillus Calmette Guérin) vaccine, Tice substrain.

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    Zhang, A; Groves, M J

    1988-09-01

    Reconstituted, lyophilized, attenuated Mycobacterium bovis, Bacillus Calmette Guérin (BCG) vaccine, Tice substrain, was characterized using a Coulter Multisizer and a HIAC/Royco counter. The primary organism has an equivalent spherical diameter approximating 1 micron but the BCG cell suspension is heavily aggregated. The cumulative size distribution of the suspension fits a log-probit plot and this information can be used to determine the total number of particles per ampoule. The instrumental count may be related to the viable count. The state of dispersion was unaffected by mild shear (syringe aspiration or ultrasound) and only slightly affected by the addition of cetylpyridinium chloride or sodium tauroglycolate. PMID:3073388

  2. Reducing the activity and secretion of microbial antioxidants enhances the immunogenicity of BCG.

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    Shanmugalakshmi Sadagopal

    Full Text Available BACKGROUND: In early clinical studies, the live tuberculosis vaccine Mycobacterium bovis BCG exhibited 80% protective efficacy against pulmonary tuberculosis (TB. Although BCG still exhibits reliable protection against TB meningitis and miliary TB in early childhood it has become less reliable in protecting against pulmonary TB. During decades of in vitro cultivation BCG not only lost some genes due to deletions of regions of the chromosome but also underwent gene duplication and other mutations resulting in increased antioxidant production. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether microbial antioxidants influence vaccine immunogenicity, we eliminated duplicated alleles encoding the oxidative stress sigma factor SigH in BCG Tice and reduced the activity and secretion of iron co-factored superoxide dismutase. We then used assays of gene expression and flow cytometry with intracellular cytokine staining to compare BCG-specific immune responses in mice after vaccination with BCG Tice or the modified BCG vaccine. Compared to BCG, the modified vaccine induced greater IL-12p40, RANTES, and IL-21 mRNA in the spleens of mice at three days post-immunization, more cytokine-producing CD8+ lymphocytes at the peak of the primary immune response, and more IL-2-producing CD4+ lymphocytes during the memory phase. The modified vaccine also induced stronger secondary CD4+ lymphocyte responses and greater clearance of challenge bacilli. CONCLUSIONS/SIGNIFICANCE: We conclude that antioxidants produced by BCG suppress host immune responses. These findings challenge the hypothesis that the failure of extensively cultivated BCG vaccines to prevent pulmonary tuberculosis is due to over-attenuation and suggest instead a new model in which BCG evolved to produce more immunity-suppressing antioxidants. By targeting these antioxidants it may be possible to restore BCG's ability to protect against pulmonary TB.

  3. Oral vaccination with lipid-formulated BCG induces a long-lived, multifunctional CD4(+ T cell memory immune response.

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    Lindsay R Ancelet

    Full Text Available Oral delivery of BCG in a lipid formulation (Liporale™-BCG targets delivery of viable bacilli to the mesenteric lymph nodes and confers protection against an aerosol Mycobacterium tuberculosis challenge. The magnitude, quality and duration of the effector and memory immune response induced by Liporale™-BCG vaccination is unknown. Therefore, we compared the effector and memory CD4(+ T cell response in the spleen and lungs of mice vaccinated with Liporale™-BCG to the response induced by subcutaneous BCG vaccination. Liporale™-BCG vaccination induced a long-lived CD4(+ T cell response, evident by the detection of effector CD4(+ T cells in the lungs and a significant increase in the number of Ag85B tetramer-specific CD4(+ T cells in the spleen up to 30 weeks post vaccination. Moreover, following polyclonal stimulation, Liporale™-BCG vaccination, but not s.c. BCG vaccination, induced a significant increase in both the percentage of CD4(+ T cells in the lungs capable of producing IFNγ and the number of multifunctional CD4(+ T cells in the lungs at 30 weeks post vaccination. These results demonstrate that orally delivered Liporale™-BCG vaccine induces a long-lived multifunctional immune response, and could therefore represent a practical and effective means of delivering novel BCG-based TB vaccines.

  4. Changes in the resistance of mice to enteral infection and prolonged irradiation induced by live BCG vaccine

    International Nuclear Information System (INIS)

    The influence of the live BCG vaccine on the antiinfection resistance to heterologic stimulus and on the radioresistance at the prolonged irradiation is studied. In the latter case mice have been induced intradermally 0.1 mg. of BCG and in 15 days they have been irradiated by 137Cs γ rays in the 1600 R dose, with 1 R/min. rate. It is concluded that under the influence of vacination by live BCG microbacteria there can occur on a certain stage of the development of immunologic process the natural resistance weakening of the body expressed in our experiments in the decrease of resistance to heterologic infection and prolonged γ ray irradiation effect in two weeks after vaccine induction

  5. Systemic BCG-Osis as a Rare Side Effect of Intravesical BCG Treatment for Superficial Bladder Cancer

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    Lukacs, S.; B. Tschobotko; Szabo, N. A.; Andrew Symes

    2013-01-01

    Intravesical Bacilli Calmette-Guérin (BCG) immunotherapy is a commonly used treatment for superficial bladder cancer. Although the treatment is well tolerated in 95% of cases, life-threatening side effects including BCG sepsis can occur. This report describes the case of an 82-year-old man with a background of lung disease. He developed septic shock and type two respiratory failure after receiving the sixth installation of intravesical BCG (TICE strain) immunotherapy for recurrent bladder Tra...

  6. Variable Virulence and Efficacy of BCG Vaccine Strains in Mice and Correlation With Genome Polymorphisms.

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    Zhang, Lu; Ru, Huan-Wei; Chen, Fu-Zeng; Jin, Chun-Yan; Sun, Rui-Feng; Fan, Xiao-Yong; Guo, Ming; Mai, Jun-Tao; Xu, Wen-Xi; Lin, Qing-Xia; Liu, Jun

    2016-02-01

    Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the only vaccine available for tuberculosis (TB) control. However, BCG is not an ideal vaccine and has two major limitations: BCG exhibits highly variable effectiveness against the development of TB both in pediatric and adult populations and can cause disseminated BCG disease in immunocompromised individuals. BCG comprises a number of substrains that are genetically distinct. Whether and how these genetic differences affect BCG efficacy remains largely unknown. In this study, we performed comparative analyses of the virulence and efficacy of 13 BCG strains, representing different genetic lineages, in SCID and BALB/c mice. Our results show that BCG strains of the DU2 group IV (BCG-Phipps, BCG-Frappier, BCG-Pasteur, and BCG-Tice) exhibit the highest levels of virulence, and BCG strains of the DU2 group II (BCG-Sweden, BCG-Birkhaug) are among the least virulent group. These distinct levels of virulence may be explained by strain-specific duplications and deletions of genomic DNA. There appears to be a general trend that more virulent BCG strains are also more effective in protection against Mycobacterium tuberculosis challenge. Our findings have important implications for current BCG vaccine programs and for future TB vaccine development. PMID:26643797

  7. BCG LYMPHADENITIS

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    Vijayakumar

    2014-08-01

    Full Text Available Background: The World Health Organization (WHO has recommended Bacillus Calmette-Guerin (BCG vaccination as a part of the global expanded program for immunization. Although the BCG vaccine is usually a safe vaccine, a number of complications with lymphadenitis being the most common complication, can occur. AIM: The aim of the present study was to evaluate the clinical presentation and the histomorphological features of BCG adenitis in children. RESULTS: A total of 60 patients with BCG lymphadenitis presented between June 2010 and December 2013. The most common age of presentation was 3 months. In the majority (50 of the cases, the lymphadenitis involved ipsilateral left axillary nodes. Other sites of involvement included the left supraclavicular lymph nodes in 5 (8.3% patients, and both the left axillary and supraclavicular lymph nodes were involved in 5 cases (8.3%. All the patients had history of BCG vaccination prior to the onset of lymphadenitis. CONCLUSION: Diagnosis of BCG lymphadenitis is clinical. Parental education and awareness among paramedical personnel, including general practitioners, is essential so that prompt recognition and management of BCG adenitis can be ensured.

  8. Role of fibronectin in intravesical BCG therapy for superficial bladder cancer.

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    Ratliff, T L; Kavoussi, L R; Catalona, W J

    1988-02-01

    Intravesical bacillus Calmette-Guerin (BCG) has been demonstrated to be effective both for prophylaxis and treatment of superficial bladder cancer. In order to identify the progression of events that result in BCG-mediated antitumor activity, studies were performed to evaluate the mechanism of binding of BCG within the bladder. Histological and quantitative studies in a mouse model revealed that BCG attached to the bladder wall only in areas of urothelial damage. Preliminary in vitro data showed that BCG attached to surfaces coated with extracellular matrix proteins. Further studies were then performed using purified extracellular matrix proteins to identify the proteins responsible for attachment. BCG were observed to attach to surfaces coated only with purified fibronectin (FN) but not to other purified proteins including laminin, collagen or fibrinogen. The attachment of BCG to purified FN in vitro was dose dependent and was inhibited by anti-FN antibodies. Moreover, BCG attachment in vivo to bladders with damaged urothelial surfaces was inhibited more than 95% by anti-FN antibodies, but binding was not affected by anti-laminin antibodies or preimmune serum. A survey of commercially available BCG vaccines (Pasteur, Tice, Glaxo, Connaught) showed that only Glaxo BCG did not attach to FN-coated surfaces. Glaxo BCG also was shown to express inferior antitumor activity suggesting that the absence of FN binding by Glaxo may have been associated with the absence of antitumor activity of the vaccine. PMID:3276931

  9. Nonclinical Development of BCG Replacement Vaccine Candidates

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    Bernd Eisele; Martin Gengenbacher; Reginald Kidd; David McCown; Sheldon Morris; Steven Derrick; David Hokey; Dominick Laddy; Rosemary Chang; Megan Fitzpatrick; Leander Grode; Kamalakannan Velmurugan; Stefan H. E. Kaufmann; John Fulkerson; Brennan, Michael J.

    2013-01-01

    The failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG) vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG) strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both ...

  10. A Modified Bacillus Calmette-Guérin (BCG Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence

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    Douglas S. Kernodle

    2013-01-01

    Full Text Available Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune suppressive capacity. We made four modifications to BCG Tice to produce 4dBCG and compared it to the parent vaccine in C57Bl/6 mice. The modifications included elimination of the oxidative stress sigma factor SigH, elimination of the SecA2 secretion channel, and reductions in the activity of iron co-factored superoxide dismutase and glutamine synthetase. After IV inoculation of 4dBCG, 95% of vaccine bacilli were eradicated from the spleens of mice within 60 days whereas the titer of BCG Tice was not significantly reduced. Subcutaneous vaccination with 4dBCG produced greater protection than vaccination with BCG against dissemination of an aerosolized challenge of M. tuberculosis to the spleen at 8 weeks post-challenge. At this time, 4dBCG-vaccinated mice also exhibited altered lung histopathology compared to BCG-vaccinated mice and control mice with less well-developed lymphohistiocytic nodules in the lung parenchyma. At 26 weeks post-challenge, 4dBCG-vaccinated mice but not BCG-vaccinated mice had significantly fewer challenge bacilli in the lungs than control mice. In conclusion, despite reduced persistence in mice a modified BCG vaccine with diminished antioxidants and glutamine synthetase is superior to the parent vaccine in conferring protection against M. tuberculosis. The targeting of multiple immune suppressive factors produced by BCG is a promising strategy for simultaneously improving vaccine safety and effectiveness.

  11. Murine immune responses to oral BCG immunization in the presence or absence of prior BCG sensitization.

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    Cross, Martin L; Lambeth, Matthew R; Aldwell, Frank E

    2010-02-01

    Oral delivery of live Mycobacterium bovis BCG in a lipid matrix invokes cell-mediated immune (CMI) responses in mice and consequent protection against pulmonary challenge with virulent mycobacteria. To investigate the influence of prior BCG sensitization on oral vaccine efficacy, we assessed CMI responses and BCG colonization of the alimentary tract lymphatics 5 months after oral vaccination, in both previously naive mice and in mice that had been sensitized to BCG by injection 6 months previously. CMI responses did not differ significantly between mice that received subcutaneous BCG followed by oral BCG and those that received either injected or oral BCG alone. In vivo BCG colonization was predominant in the mesenteric lymph nodes after oral vaccination; this colonizing ability was not influenced by prior BCG sensitization. From this murine model study, we conclude that although prior parenteral-route BCG sensitization does not detrimentally affect BCG colonization after oral vaccination, there is no significant immune-boosting effect of the oral vaccine either. PMID:19918257

  12. Mycobacterium bovis BCG priming induces a strong potentiation of the antibody response induced by recombinant BCG expressing a foreign antigen.

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    Gheorghiu, M; Lagranderie, M R; Gicquel, B M; Leclerc, C D

    1994-01-01

    Several recent studies have demonstrated that strong cellular or humoral immune responses can be induced against foreign antigens expressed by recombinant Mycobacterium bovis BCG. It has therefore been suggested that BCG could represent one of the best candidate vectors for live recombinant vaccines. However, a large percentage of the human population has been immunized by BCG, and this priming could modify the immune response to future recombinant BCG vaccines. In the present study, we have ...

  13. Systemic BCG-Osis as a Rare Side Effect of Intravesical BCG Treatment for Superficial Bladder Cancer

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    S. Lukacs

    2013-01-01

    Full Text Available Intravesical Bacilli Calmette-Guérin (BCG immunotherapy is a commonly used treatment for superficial bladder cancer. Although the treatment is well tolerated in 95% of cases, life-threatening side effects including BCG sepsis can occur. This report describes the case of an 82-year-old man with a background of lung disease. He developed septic shock and type two respiratory failure after receiving the sixth installation of intravesical BCG (TICE strain immunotherapy for recurrent bladder Transitional Cell Carcinoma in situ. Despite the early initiation of broad spectrum antibiotics (tazocin and gentamicin, he remained pyrexial. There was a rapid deterioration, and on the second day of his admission, he developed type two respiratory failure secondary to Acute Respiratory Distress Syndrome (ARDS prompting transfer to Intensive Care for Bilevel Positive Airway Pressure (BiPAP Ventilation. The blood cultures taken before the induction of antibiotics results were negative. Increasing clinical suspicion of systemic BCG-osis prompted the initiation of antituberculosis therapy (ethambutol, isoniazid rifampicin and steroids. Following six days of BiPAP and anti-tuberculosis therapy in ITU, his condition started to improve. Following a prolonged hospital stay he was discharged on long term ethambutol therapy. BCG-osis is a well-known though rare side effect of intravesical BCG therapy. We would like to highlight the importance of having a low threshold for starting anti-TB treatment.

  14. Systemic BCG-Osis as a Rare Side Effect of Intravesical BCG Treatment for Superficial Bladder Cancer.

    Science.gov (United States)

    Lukacs, S; Tschobotko, B; Szabo, N A; Symes, Andrew

    2013-01-01

    Intravesical Bacilli Calmette-Guérin (BCG) immunotherapy is a commonly used treatment for superficial bladder cancer. Although the treatment is well tolerated in 95% of cases, life-threatening side effects including BCG sepsis can occur. This report describes the case of an 82-year-old man with a background of lung disease. He developed septic shock and type two respiratory failure after receiving the sixth installation of intravesical BCG (TICE strain) immunotherapy for recurrent bladder Transitional Cell Carcinoma in situ. Despite the early initiation of broad spectrum antibiotics (tazocin and gentamicin), he remained pyrexial. There was a rapid deterioration, and on the second day of his admission, he developed type two respiratory failure secondary to Acute Respiratory Distress Syndrome (ARDS) prompting transfer to Intensive Care for Bilevel Positive Airway Pressure (BiPAP) Ventilation. The blood cultures taken before the induction of antibiotics results were negative. Increasing clinical suspicion of systemic BCG-osis prompted the initiation of antituberculosis therapy (ethambutol, isoniazid rifampicin) and steroids. Following six days of BiPAP and anti-tuberculosis therapy in ITU, his condition started to improve. Following a prolonged hospital stay he was discharged on long term ethambutol therapy. BCG-osis is a well-known though rare side effect of intravesical BCG therapy. We would like to highlight the importance of having a low threshold for starting anti-TB treatment. PMID:23844314

  15. Nonclinical Development of BCG Replacement Vaccine Candidates.

    Science.gov (United States)

    Velmurugan, Kamalakannan; Grode, Leander; Chang, Rosemary; Fitzpatrick, Megan; Laddy, Dominick; Hokey, David; Derrick, Steven; Morris, Sheldon; McCown, David; Kidd, Reginald; Gengenbacher, Martin; Eisele, Bernd; Kaufmann, Stefan H E; Fulkerson, John; Brennan, Michael J

    2013-01-01

    The failure of current Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG) strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO) from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO) from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines. PMID:26343962

  16. Nonclinical Development of BCG Replacement Vaccine Candidates

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    Bernd Eisele

    2013-04-01

    Full Text Available The failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines.

  17. BCG vaccine in Korea

    OpenAIRE

    Joung, Sun Myung; Ryoo, Sungweon

    2013-01-01

    The anti-tuberculosis Bacille de Calmette et Guérin (BCG) vaccine was developed between 1905 and 1921 at Pasteur Institutes of Lille in France, and was adopted by many countries. BCG strains comprise natural mutants of major virulence factors of Mycobacterium tuberculosis and that BCG sub-strains differ markedly in virulence levels. The tuberculosis became endemic in Korea after the Korean War (1950s). The BCG strain, which was donated by Pasteur Institutes, was brought to Korea in 1955, and ...

  18. Role for Gr-1+ Cells in the Control of High-Dose Mycobacterium bovis Recombinant BCG

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    Panas, Michael W.; Letvin, Norman L.

    2014-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) is an attractive target for development as a live vaccine vector delivering transgenic antigens from HIV and other pathogens. Most studies aimed at defining the clearance of BCG have been performed at doses between 102 and 104 CFU. Interestingly, however, recombinant BCG (rBCG) administered at doses of >106 CFU effectively generates antigen-specific T-cell responses and primes for heterologous boost responses. Thus, defining clearance at high...

  19. Tuberculosis: looking beyond BCG vaccines.

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    Mustafa Abu S

    2003-01-01

    Full Text Available Tuberculosis (TB is an infectious disease of international importance and ranks among the top 10 causes of death in the World. About one-third of the world′s population is infected with Mycobacterium tuberculosis. Every year, approximately eight million people develop active disease and two million die of TB. The currently used BCG vaccines have shown variable protective efficacies against TB in different parts of the world. Moreover, being a live vaccine, BCG can be pathogenic in immunocompromised recipients. Therefore, there is an urgent need to develop new vaccines against TB. The comparative genome analysis has revealed the existence of several M. tuberculosis-specific regions that are deleted in BCG. The work carried out to determine the immunological reactivity of proteins encoded by genes located in these regions revealed several major antigens of M. tuberculosis, including the 6 kDa early secreted antigen target (ESAT6. Immunization with ESAT6 and its peptide (aa51-70 protects mice challenged with M. tuberculosis. The protective efficacy of immunization further improves when ESAT6 is recombinantly fused with M. tuberculosis antigen 85B. In addition, ESAT6 delivered as a DNA vaccine is also protective in mice. Whether these vaccines would be safe or not cannot be speculated. The answer regarding the safety and efficacy of these vaccines has to await human trials in different parts of the world.

  20. BCG ADENITIS: ACTION OR INACTION?

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    Ashwin V; Shruti; De, Dipankar

    2014-01-01

    BCG adenitis, the enlargement of regional lymph nodes after BCG vaccination is one of the common complications seen. BCG adenitis may present at varied time interval after the vaccine administration. Different medical and surgical treatment modalities have been reported for its management. We report our management experience of BCG adenitis seen over a period of 1 year.

  1. Mycobacterium bovis BCG Vaccines Exhibit Defects in Alanine and Serine Catabolism

    OpenAIRE

    Chen, Jeffrey M.; Alexander, David C.; Behr, Marcel A.; LIU Jun

    2003-01-01

    Mycobacterium bovis BCG is the only accepted vaccine for the prevention of tuberculosis (TB) in humans. BCG is a live vaccine, and induction of immunity to TB requires productive infection of the host by BCG. However, BCG is not a satisfactory vaccine, because it fails to protect against pulmonary TB in adults. In this study, we found that BCG strains cannot utilize many naturally occurring amino acids as the sole nitrogen source for growth. This defect is caused, at least partially, by the l...

  2. BCG lymphadenopathy detected in a BCG-vaccinated infant

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    A.S. Barouni

    2004-05-01

    Full Text Available Large-scale vaccination with BCG, the live attenuated strain of Mycobacterium bovis, is being adopted around the world, although sporadic complications have occurred after the procedure. Lymphadenopathy is not uncommon especially in babies under one year (0.73% of vaccinated infants, but the swelling subsides within 2 months in most cases, with no medical or surgical treatment. Brazil adopted BCG vaccination program earlier in the seventies and by 1995 more than 96% of the infant population received this immunization. We report here the occurrence of lymphadenopathy in a two-year-old child vaccinated with the Brazilian BCG strain. The diagnosis was made using a lymph node biopsy and intestinal aspirates that yielded a positive mycobacterial culture. The isolate was resistant to isoniazid, rifampicin, pyrazinamide and thiophen-2-carbonic acid hydrazide, sensitive to streptomycin, ethambutol, and p-nitrobenzoic acid, and reacted positively to cyclo-serine and negatively to niacin. The pncA gene involved in bacterial activation of pyrazinamide contains in M. bovis a point mutation that renders pyrazinamidase unable to catalyze drug activation. Therefore, this polymorphism is a good option for developing methods to differentiate M. bovis and M. tuberculosis. Taking advantage of this difference we further analyzed the isolates by single-stranded conformation polymorphism electrophoresis of DNA following PCR of the pncA gene. The isolate identity was confirmed by RFLP electrophoretic analysis of the amplified fragment following Eco065I digestion, which selectively cleaves M. tuberculosis DNA. From this result it is proposed that RFLP of pncA gene represents an alternative for differential diagnosis of M. bovis.

  3. The future of neonatal BCG.

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    Odent, Michel R

    2016-06-01

    -up. Furthermore, whatever the standard of living of the populations and the research protocols, concordant results suggest that BCG has positive non-specific long term effects on health. Meanwhile, some simple adaptive practices are possible, such as, after a caesarean section, wrapping the neonate in clothes recently worn by the mother and, occasionally, putting the neonate in the arms of a person who is cohabiting with the mother. PMID:27142139

  4. Prime-boost vaccination strategy with bacillus Calmette-Guérin (BCG) and liposomized alpha-crystalline protein 1 reinvigorates BCG potency.

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    Siddiqui, K F; Amir, M; Khan, N; Rama Krishna, G; Sheikh, J A; Rajagopal, K; Agrewala, J N

    2015-08-01

    Bacillus Calmette-Guérin (BCG) remains the only available and most widely administered vaccine against Mycobacterium tuberculosis (Mtb), yet it fails to protect vaccinated individuals either from primary infection or reactivation of latent tuberculosis (TB). Despite BCG's variable efficacy against TB, the fact remains that BCG imparts protection in children against the disease, indicating that BCG possesses a wide protective antigenic repertoire. However, its failure to impart protection in adulthood can be linked to its failure to generate long-lived memory response and elicitation of an inadequate immune response against latency-associated antigens. Therefore, to improve the protective efficacy of BCG, a novel vaccination strategy is required. Consequently, in the present study, we have exploited the vaccination potential of liposomized α-crystalline 1 (Acr1L), a latency-associated antigen to induce enduring protective immunity against Mtb in BCG-primed animals. It is noteworthy that an increase in the multi-functional [interferon (IFN)-γ(hi) /tumour necrosis factor (TNF)-α(hi) ] CD4 and CD8 T cells were observed in BCG-primed and Acr1L-boosted (BCG-Acr1L) animals, compared to BCG alone. Further, substantial expansion of both central memory (CD44(hi) /CD62L(hi) ) and effector memory (CD44(hi) /CD62L(lo) ) populations of CD4 and CD8 T cells was noted. Importantly, BCG-Acr1L exhibited significantly better protection than BCG, as evidenced by a reduction in the bacterial burden and histopathological data of the lungs. In essence, BCG-Acr1L could be a potent future vaccination strategy to reinvigorate BCG potency. PMID:25845290

  5. Bacillus Calmette-Guerin (BCG) Vaccine

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    TheraCys® BCG ... TICE® BCG ... WHY is this medicine prescribed?BCG vaccine provides immunity or protection against tuberculosis (TB). The vaccine may be given to persons at high risk of developing TB. ...

  6. Spleen cell cytokine secretion in Mycobacterium bovis BCG-infected mice.

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    Huygen, K.; Abramowicz, D.; Vandenbussche, P; Jacobs, F.; De Bruyn, J; Kentos, A.; Drowart, A; van Vooren, J P; Goldman, M.

    1992-01-01

    Three susceptible mouse strains, i.e., BALB/c (H-2d), C57BL/6 (H-2b), and major histocompatibility complex-congenic BALB.B10 (H-2b), were infected intravenously with 4 x 10(6) CFU of live Mycobacterium bovis BCG and analyzed 4 weeks later for in vitro spleen cell cytokine secretion in response to purified protein derivative (PPD), BCG culture filtrate (CF), BCG cellular extract, total BCG, the purified extracellular 30-32-kDa antigen (the fibronectin-binding antigen 85), or the intracellular ...

  7. Visible and subvisible particles in the BCG immunotherapeutic product Immucyst®

    Science.gov (United States)

    Kirkitadze, Marina; Remi, Elena; Bhandal, Kamajit; Carpick, Bruce

    2016-01-01

    Bacille Calmette–Guerin, BCG, is a live attenuated bovine tubercle bacillus used for the treatment of non-muscle invasive bladder cancer. In this study, an Electrical Sensing Zone (ESZ) method was developed to measure the particle count and the size of BCG immunotherapeutic (BCG IT), or ImmuCyst® product using a Coulter Counter Multisizer 4® instrument. The focus of this study was to establish a baseline for reconstituted lyophilized BCG IT product using visible and sub-visible particle concentration and size distribution as reportable values. ESZ method was used to assess manufacturing process consistency using 20 production scale lots of BCG IT product. The results demonstrated that ESZ can be used to accumulate product and process knowledge of BCG IT. PMID:27158432

  8. Visible and subvisible particles in the BCG immunotherapeutic product Immucyst®.

    Science.gov (United States)

    Kirkitadze, Marina; Remi, Elena; Bhandal, Kamajit; Carpick, Bruce

    2016-01-01

    Bacille Calmette-Guerin, BCG, is a live attenuated bovine tubercle bacillus used for the treatment of non-muscle invasive bladder cancer. In this study, an Electrical Sensing Zone (ESZ) method was developed to measure the particle count and the size of BCG immunotherapeutic (BCG IT), or ImmuCyst® product using a Coulter Counter Multisizer 4® instrument. The focus of this study was to establish a baseline for reconstituted lyophilized BCG IT product using visible and sub-visible particle concentration and size distribution as reportable values. ESZ method was used to assess manufacturing process consistency using 20 production scale lots of BCG IT product. The results demonstrated that ESZ can be used to accumulate product and process knowledge of BCG IT. PMID:27158432

  9. The effect of tuberculin skin test and BCG vaccination on the expansion of PPD-specific IFN-gamma producing cells ex vivo.

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    Ota, Martin O C; Brookes, Roger H; Hill, Philip C; Owiafe, Patrick K; Ibanga, Hannah B; Donkor, Simon; Awine, Timothy; McShane, Helen; Adegbola, Richard A

    2007-12-17

    Understanding the immunogenicity of BCG in a population where it has failed will facilitate the design of new TB vaccines. We assessed the immunogenicity of M. bovis BCG over 12 months by ELISPOT assay. Forty-one adolescents and young Gambian male adults received a tuberculin skin test (TST) which was followed one week later by BCG vaccination, but the 23 control subjects received neither of these. TST alone significantly induced PPD-specific IFN-gamma producing cells. Twenty-three percent of subjects did not respond to BCG, which was associated with higher pre-existing ex vivo response to PPD. Paradoxically, amongst BCG responders there was a correlation between pre-existing response and subsequent response to BCG. We conclude that BCG is immunogenic, but this effector response is short-lived and can be limited in higher pre-existing anti-mycobacterial immunity, suggesting a possible threshold beyond which BCG immunogenicity is inhibited. PMID:18023944

  10. Improvements in the BCG code

    International Nuclear Information System (INIS)

    Some improvements introduced in the BCG code with the objective of making the code faster in execution are reported. The impact of these improvements in terms of CPU time saving is discussed for a sample problem. (author)

  11. Ultrasonographic features of BCG lymphadenitis

    International Nuclear Information System (INIS)

    To evaluate the ultrasonographic findings of BCG lymphadenitis complicated by BCG vaccination in children. Ultrasonography was performed for 22 cases of BCG lymphadenitis in 21 patients who were diagnosed by clinical (n=10) or pathological (n=11) examinations. Their age ranged from 4 months to 3 years (mean age; 14 months). We retrospectively analyzed the ultrasonographic findings for location, multiplicity, size, shape, margin, echogenecity, posterior enhancement, calcifications, inner anechoic portion and Doppler pattern of the BCG lymphadenitis. The BCG lymphadenitis was found at the axillary area in 15 cases (68%) and at the supraclavicular area in 7 cases (32%). There were ten cases (45%) of solitary lesion and 12 cases (55%) of multiple conglomerated lesions. The maximum diameter ranged from about 0.9 cm to 3.2 cm. The BCG lymphadenitis showed as round (82%), well defined (86%), or heterogeneous hypoechoic (68%) lesions with posterior enhancement (78%). Calcifications were found in 6 cases (27%) and 5 cases (83%) had been vaccinated more than 5 months ago. There were eccentric inner anechoic portions in 16 cases (73%), which were pathologically confirmed as having caseating necrosis. There were increased Doppler flow patterns in 15 cases (68%); 4 cases (18%) were of the central type, 6 cases (27%) were of the peripheral type and 5 cases (23%) were of mixed type. BCG lymphadenitis is frequently located at the axillary area adjacent to a vaccination site. The ultrasonographic findings of BCG lymphadenitis are well-defined, round, heterogeneously hypoechoic lesions with posterior enhancement, calcifications and inner eccentric anechoic portion

  12. Digestive juices action on the absorption and the oral BCG destination

    International Nuclear Information System (INIS)

    The absorption and the biological routing of Mycobacterium bovis BCG vaccine following intragastric administration to mice was studied. A harmful action of gastric (GJ) and duodenal juices (DJ) on BCG cells in vitro was found. Treatment with GJ induced a significant decrease of the oxygen uptake and a moderate loss of viability as expressed by the number of colony-forming units (CFU) of BCG. Severe decreases of bacilli respiration and a notable fall of CFU counts were detected during DJ treatment. The biorouting of BCG cells was determined using carbon-14 labelled bacilli. The labelling was accomplished through a metabolic precursor of mycobacterial lipids, sup(14)C-glycerol. The levels of radioactivity recovered at the first day in the organs of mice receiving either gastric instillation of sup(14)C-BCG, sonically disrupted sup(14)-BCG or sup(14)C glycerol were very similar. Subsequently, sonicated sup(14)C-BCG and sup(14)C-glycerol were involved in a biological decay process, while the level of sup(14)C-BCG associated radioactivity remained stable in the organs from 6 to 24 days. Data on the biodecay from the small intestine and liver showed that absorptive events were fast enough to reach the highest level at 24 hours, dropping thereafter according to the complexity of the material given to the mice. In all instances, however, living BCG was not cultured from organs of mice given unlabelled BCG. The preceding data suggest that the great majority of BCG cells that passed the gut barriers were absorbed intact but not alive. (author)

  13. Chest wall granuloma associated with BCG vaccination presenting as hot abscess in an immunocompetent infant.

    Science.gov (United States)

    Lee, Hyun Seung; Seo, Kyung Jin; Kim, Jae Jun

    2015-01-01

    Bacillus-Calmette-Gue´rin (BCG) vaccine is a live attenuated vaccine to prevent tuberculosis by cell mediated immune response and is routinely administered early after birth. Although it is considered to be a very safe vaccine, sometimes a variety of complications may develop. Herein we describe a clinically unusual case of chest wall granuloma considered to be induced by BCG, presenting as hot abscess, and developed 7 months after BCG vaccination in an immunocompetent infant. The diagnosis was made based on the history, histopathology and virological studies. We suggest, although very rare, a BCG disease should be considered as a differential diagnosis in case of chest wall abscess, even if this is presenting as a hot abscess and even in immunocompetent infants if their age is related to BCG vaccination complications. PMID:25887440

  14. Failure of the Mycobacterium bovis BCG Vaccine: Some Species of Environmental Mycobacteria Block Multiplication of BCG and Induction of Protective Immunity to Tuberculosis

    OpenAIRE

    Brandt, L.; cunha, jf; olsen, aw; Chilima, B.; Hirsch, P; Appelberg, R; Andersen, P.

    2002-01-01

    The efficacy of Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccine against pulmonary tuberculosis (TB) varies enormously in different populations. The prevailing hypothesis attributes this variation to interactions between the vaccine and mycobacteria common in the environment, but the precise mechanism has so far not been clarified. Our study demonstrates that prior exposure to live environmental mycobacteria can result in a broad immune response that is recalled rapidly after BCG va...

  15. Development of a BCG challenge model for the testing of vaccine candidates against tuberculosis in cattle.

    Science.gov (United States)

    Villarreal-Ramos, Bernardo; Berg, Stefan; Chamberlain, Laura; McShane, Helen; Hewinson, R Glyn; Clifford, Derek; Vordermeier, Martin

    2014-09-29

    Vaccination is being considered as part of a sustainable strategy for the control of bovine tuberculosis (BTB) in the UK. The live attenuated Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been used experimentally to vaccinate cattle against BTB. However, BCG confers partial protection against BTB and therefore, there is a need to develop improved vaccines. BTB vaccine efficacy experiments require the use of biosafety level 3 facilities which are expensive to maintain, generally oversubscribed and represent a bottle neck for the testing of vaccine candidates. One indicator of the induction of protective responses would be the ability of the host's immune response to control/kill mycobacteria. In this work we have evaluated an intranodal BCG challenge for the selection of vaccine candidates at biosafety level 2 which are capable of inducing mycobactericidal responses. To our knowledge, this is the first such report. Whilst BCG only confers partial protection, it is still the standard against which other vaccines are judged. Therefore we tested the BCG intranodal challenge in BCG (Danish strain) vaccinated cattle and showed that vaccinated cattle had lower BCG cfu counts than naïve cattle at 14 and 21 days after intranodal challenge with BCG (Tokyo strain). This model could help prioritize competing TB vaccine candidates and exploration of primary and secondary immune responses to mycobacteria. PMID:25138291

  16. BCG Δzmp1 vaccine induces enhanced antigen specific immune responses in cattle.

    Science.gov (United States)

    Khatri, Bhagwati; Whelan, Adam; Clifford, Derek; Petrera, Agnese; Sander, Peter; Vordermeier, H Martin

    2014-02-01

    Mycobacterium bovis (M. bovis) causes major economy and public health problem in numerous countries. In Great Britain, despite the use of a test-and-slaughter strategy, the incidence of bovine tuberculosis (bTB) in cattle has steadily risen in recent years. One strategy being considered to reduce the burden of bTB in cattle is the development of an efficient vaccine. The only current potentially available vaccine against tuberculosis, live attenuated M. bovis bacille Calmette-Guérin (BCG), has demonstrated variable efficacy in both humans and cattle and the development of improved vaccination strategies for cattle is a research priority. In this study we assessed the immunogenicity in cattle of two recombinant BCG strains, namely BCG Pasteur Δzmp1::aph and BCG Danish Δzmp1. By applying a recently defined predictive immune-correlate of protection (T cell memory responses measured by cultured ELISPOT), we have compared these two recombinant BCG with wild-type BCG Danish SSI. Our results demonstrated that both strains induced superior T cell memory responses compared to wild-type BCG. These data provide support for the prioritisation of testing BCG Danish Δzmp1 in vaccination/M. bovis challenge studies to determine its protective efficacy. PMID:24394444

  17. Long-term in vitro and in vivo effects of γ-irradiated BCG on innate and adaptive immunity

    DEFF Research Database (Denmark)

    Arts, Rob J W; Blok, Bastiaan A; Aaby, Peter; Joosten, Leo A B; de Jong, Dirk; van der Meer, Jos W M; Benn, Christine Stabell; van Crevel, Reinout; Netea, Mihai G

    2015-01-01

    BCG vaccination is associated with a reduced mortality from nonmycobacterial infections. This is likely to be mediated by a combination of innate-immune memory ("trained immunity") and heterologous effects on adaptive immunity. As such, BCG could be used to boost host immunity but not in...... immunocompromised hosts, as it is a live, attenuated vaccine. Therefore, we assessed whether killed γBCG has similar potentiating effects. In an in vitro model of trained immunity, human monocytes were incubated with γBCG for 24 h and restimulated after 6 d. Cytokine production and the role of pattern recognition...... receptors and histone methylation markers were assessed. The in vivo effects of γBCG vaccination were studied in a proof-of-principle trial in 15 healthy volunteers. γBCG induced trained immunity in vitro via the NOD2 receptor pathway and up-regulation of H3K4me3 histone methylation. However, these effects...

  18. Heaf test results after neonatal BCG.

    OpenAIRE

    Crawshaw, P. A.; Thomson, A H

    1988-01-01

    Heaf testing was carried out on 98 preschool Asian children who had received a BCG vaccination. A strongly positive Heaf reaction (grade 3) occurred in only two children. Heaf testing can still be used in tuberculosis screening after neonatal BCG.

  19. Tuberculous Meningitis in BCG-Vaccinated Children

    Directory of Open Access Journals (Sweden)

    M Movahhedi

    1998-05-01

    Full Text Available It is generally accepted that BCG vaccination is fully effective in preventing Tuberculous Meningitis and military Tuberculous, although it does not develop complete immunity for Tuberculous infection of lungs and other organs. A series of 3 children with Tuberculous Meningitis who had positive history of BCG vaccination as newborns and distinct BCG scar show that Tuberculous Meningitis may be caught despite successful BCG vaccination.

  20. Li intercalation in transparent Ti-Ce oxide films: Energetics and ion dynamics

    Science.gov (United States)

    Mattsson, M. Stro/mme; Azens, A.; Niklasson, G. A.; Granqvist, C. G.; Purans, J.

    1997-05-01

    Films of Ti dioxide, mixed Ti-Ce oxide, and Ce dioxide were produced by reactive dc magnetron sputtering. Electrochemical lithiation was probed by chronopotentiometry, cyclic voltammetry together with optical transmittance recording, and impedance spectroscopy. Evidence was found for inserted electrons being accommodated in Ce 4f states; this contention was supported by preliminary results from x-ray absorption fine-structure spectroscopy. These electrons do not produce luminous electrochromism. The variation of the chemical diffusion coefficient of Li, with film composition and Li content, was also studied.

  1. Systemic BCG infection in a patient with pancytopaenia and fever 9 years after intravesical BCG administration for bladder cancer.

    Science.gov (United States)

    Westhovens, Ine M; Vanden Abeele, Marie-Elena; Messiaen, Peter E; van der Hilst, Jeroen Ch

    2016-01-01

    BCG is an attenuated live strain of Mycobacterium bovis that is used as an intravesical immunotherapy for superficial bladder cancer. Although generally well tolerated, BCG instillation can lead to systemic diseases. We present a case of a 75-year-old man who was treated for recurrent localised transitional cell carcinoma (TCC) of the bladder with intravesical instillation of BCG in 2006. His medical history included Parkinson's disease. The patient reported worsening of Parkinson symptoms in the preceding month. In addition, he had progressive pancytopaenia and a bone marrow biopsy showed a granulomatous inflammatory infiltrate. Cultures from bone marrow aspiration grew M. bovis He was successfully treated with tuberculostatic drugs and made a full recovery. In addition, there was partial amelioration of the Parkinson symptoms. This case shows that physicians should be aware that BCG instillation for TCC can cause systemic disease even years after treatment. PMID:27170615

  2. Osteíte por BCG Osteitis after BCG vaccination

    Directory of Open Access Journals (Sweden)

    André Fukunishi Yamada

    2009-03-01

    Full Text Available Os autores relatam o caso de um menino de 1 ano e 9 meses que apresentou lesão osteolítica na região proximal do úmero direito. Com base na história clínica e em achados histológicos, os autores suspeitaram de osteíte pósvacina BCG. Após o início do tratamento antituberculose, os sintomas desapareceram e o paciente apresentou melhora radiológica. Os autores descrevem esta entidade incomum na prática pediátrica e alertam para possíveis complicações da vacina BCG.The authors report the case of a 21-month-old boy with an osteolytic lesion in the proximal region of the right humerus. Based on the clinical history and histological findings, the authors suspected osteitis following BCG vaccination. Symptoms remitted after antituberculosis therapy was initiated, and the patient presented radiological improvement. The authors describe this uncommon entity in pediatric practice and call attention to possible complications of BCG vaccination.

  3. WHO Informal Consultation on standardization and evaluation of BCG vaccines Geneva, Switzerland 22-23 September 2009.

    Science.gov (United States)

    Ho, Mei M; Southern, James; Kang, Hye-Na; Knezevic, Ivana

    2010-10-01

    The current World Health Organization Requirements for BCG vaccine are in need of revision to address the diversity of sub-strains used for production, potential improvements of quality control assays for lot release, and the establishment of sub-strain specific Reference Reagents. A consultation meeting was organized to discuss issues regarding the standardization and evaluation of BCG vaccines in the forum of regulators, BCG vaccine manufacturers, developers of selected new live tuberculosis (TB) vaccines and researchers. The development of new recombinant BCG and live attenuated TB vaccines and the characterisation of different BCG sub-strains using state-of-the-art technologies were also reviewed. The objective of the meeting was to revise and update the current recommendations focused on the scope, terminology, manufacturing issues, and the incorporation of new reference reagents and new quality control tests. PMID:20692219

  4. Presence of mycobacterial L-forms in human blood: Challenge of BCG vaccination

    OpenAIRE

    Markova, Nadya; Slavchev, Georgi; Michailova, Lilia

    2015-01-01

    Possible persistence of bacteria in human blood as cell wall deficient forms (L-forms) represents a top research priority for microbiologists. Application of live BCG vaccine and L-form transformation of vaccine strain may display a new intriguing aspect concerning the opportunity for occurrence of unpredictable colonization inside the human body by unusual microbial life forms. L-form cultures were isolated from 141 blood samples of people previously vaccinated with BCG, none with a history ...

  5. Tuberculosis vaccine strain Mycobacterium bovis BCG Russia is a natural recA mutant

    Directory of Open Access Journals (Sweden)

    Böttger Erik C

    2008-07-01

    Full Text Available Abstract Background The current tuberculosis vaccine is a live vaccine derived from Mycobacterium bovis and attenuated by serial in vitro passaging. All vaccine substrains in use stem from one source, strain Bacille Calmette-Guérin. However, they differ in regions of genomic deletions, antigen expression levels, immunogenicity, and protective efficacy. Results As a RecA phenotype increases genetic stability and may contribute restricting the ongoing evolution of the various BCG substrains while maintaining their protective efficacy, we aimed to inactivate recA by allelic replacement in BCG vaccine strains representing different phylogenetic lineages (Pasteur, Frappier, Denmark, Russia. Homologous gene replacement was achieved successfully in three out of four strains. However, only illegitimate recombination was observed in BCG substrain Russia. Sequence analyses of recA revealed that a single nucleotide insertion in the 5' part of recA led to a translational frameshift with an early stop codon making BCG Russia a natural recA mutant. At the protein level BCG Russia failed to express RecA. Conclusion According to phylogenetic analyses BCG Russia is an ancient vaccine strain most closely related to the parental M. bovis. We hypothesize that recA inactivation in BCG Russia occurred early and is in part responsible for its high degree of genomic stability, resulting in a substrain that has less genetic alterations than other vaccine substrains with respect to M. bovis AF2122/97 wild-type.

  6. The BCG World Atlas: A Database of Global BCG Vaccination Policies and Practices

    OpenAIRE

    2011-01-01

    Madhu Pai and colleagues introduce the BCG World Atlas, an open access, user friendly Web site for TB clinicians to discern global BCG vaccination policies and practices and improve the care of their patients.

  7. Tuberculous spondylitis following BCG vaccination

    International Nuclear Information System (INIS)

    A case of a rare form of BCG osteomyelitis in the spine is presented. After vaccination, the disease started with a lymphadenitis. Later an abscess extended from the pelvic along the psoas muscles into the retroperitoneum. The soft tissue mass extended paraspinally and epidural involvement was also apparent. The vertebral involvement was detected by CT. The radiological findings are discussed with reference to the literature. (orig.)

  8. Tuberculin reaction and BCG scar

    DEFF Research Database (Denmark)

    Timmermann, Clara Amalie Gade; Biering-Sørensen, Sofie; Aaby, Peter;

    2015-01-01

    rate ratio (MRR) comparing children with a BCG scar with those without was 0.42 (95% CI = 0.19; 0.93). There was a similar tendency for TST positivity: MRR = 0.47 (95% CI = 0.14; 1.54). For LBW children who had both a positive TST reaction and a scar, the MRR was 0.22 (95% CI = 0.05; 0.87). For NBW...

  9. POPULATION ANALYSIS OF THE LOCAL ENDANGERED PŘEŠTICE BLACK-PIED PIG BREED

    Directory of Open Access Journals (Sweden)

    Emil Krupa

    2015-09-01

    Full Text Available The pedigree analysis of the local endangered Přeštice Black-Pied pig breed (n=19 289 was performed. Animals born within the period 2012-2014 were assumed as the reference population (n=1 374. The pedigree completeness index reached 100% for four generations back. The 100 % of the genetic pool was explained by 66 ancestors. Although all animals of the reference population were inbred, 57% of them had inbreeding less than five percent. Average inbreeding, co-ancestry coefficient and rate of inbreeding reached 4.93%, 13.48% and 1.29% in reference population, respectively. The effective population size calculated by four different methods varied from 32 to 91 animals in 2014. Average generation interval, average family size for sire and dam parents was 2.5, 17.46 and 6.5 animals, respectively. Total number of founders, effective number of founders, effective number of founders’ genomes and effective number of non-founders genomes reached values 299, 98.05, 21.92 and 28.23 founders, respectively. The average genetic diversity (GD loss was 13.71% in reference population. The GD loss has increased within the last three year period mainly due to the random genetic drift (77.6% and by unequal contribution of founders (22.4%. The Preštice Black-Pied breed is highly endangered with GD loss. Mating of closely related animals has to be prevented in breeding and mating program of this breed.

  10. BCG for carcinoma in situ.

    Science.gov (United States)

    Jakse, G

    1992-01-01

    Bacillus Calmette-Guérin (BCG) is the most effective intravesical therapy of carcinoma in situ of the urinary bladder. Six, weekly instillations of BCG result in a complete remission in about 70-80% of patients. The optimal dose however has still to be defined, and the value of maintenance therapy is also a matter of debate. Recurrent tumours after complete remission occur mainly in the distal ureter and prostatic urethra. In these patients, cystectomy may be required. In about 60-80% of patients, local (e.g. cystitis) and/or systemic (e.g. fever, malaise) side effects are observed. The occurrence of cystitis is associated with the number of instillations, BCG dose and a positive skin test. Systemic side effects are connected with pre-existing dysuria or bacterial cystitis and with traumatic catheterization. Severe toxicity occurs in about 5% of the patients. Prognostic parameters indicating complete remission have yet to be determined, but there is evidence that cytokines detected in the urine and immune-cell infiltration into the bladder wall revealed by immunohistochemistry, can be of value in this respect. PMID:1396945

  11. PCR identification of Mycobacterium bovis BCG.

    OpenAIRE

    Talbot, E. A.; Williams, D L; Frothingham, R

    1997-01-01

    The attenuated bacillus Calmette-Guérin (BCG) vaccine strain is derived from a virulent strain of Mycobacterium bovis. BCG is difficult to differentiate from other strains of M. bovis and other members of the M. tuberculosis complex by conventional methods. Recently, a genomic region designated RD1 was found to be present in all virulent M. bovis and M. tuberculosis strains tested but deleted from all BCG strains tested. With this information, a multiplex PCR method was developed to detect th...

  12. BCG coverage and barriers to BCG vaccination in Guinea-Bissau

    DEFF Research Database (Denmark)

    Thysen, Sanne Marie; Byberg, Stine; Pedersen, Marie; Rodrigues, Amabelia; Ravn, Henrik; Martins, Cesario; Benn, Christine Stabell; Aaby, Peter; Fisker, Ane Bærent

    2014-01-01

    BACKGROUND: BCG vaccination is recommended at birth in low-income countries, but vaccination is often delayed. Often 20-dose vials of BCG are not opened unless at least ten children are present for vaccination ("restricted vial-opening policy"). BCG coverage is usually reported as 12-month coverage......, not disclosing the delay in vaccination. Several studies show that BCG at birth lowers neonatal mortality. We assessed BCG coverage at different ages and explored reasons for delay in BCG vaccination in rural Guinea-Bissau. METHODS: Bandim Health Project (BHP) runs a health and demographic...... visits in selected intervention regions. Factors associated with delayed BCG vaccination were evaluated using logistic regression models. Coverage between intervention and control regions were evaluated in log-binomial regression models providing prevalence ratios. RESULTS: Among 3951 children born in...

  13. Recombinant BCG Expressing Mycobacterium ulcerans Ag85A Imparts Enhanced Protection against Experimental Buruli ulcer.

    Science.gov (United States)

    Hart, Bryan E; Hale, Laura P; Lee, Sunhee

    2015-09-01

    Buruli ulcer, an emerging tropical disease caused by Mycobacterium ulcerans (MU), is characterized by disfiguring skin necrosis and high morbidity. Relatively little is understood about the mode of transmission, pathogenesis, or host immune responses to MU infection. Due to significant reduction in quality of life for patients with extensive tissue scarring, and that a disproportionately high percentage of those affected are disadvantaged children, a Buruli ulcer vaccine would be greatly beneficial to the worldwide community. Previous studies have shown that mice inoculated with either M. bovis bacille Calmette-Guérin (BCG) or a DNA vaccine encoding the M. ulcerans mycolyl transferase, Ag85A (MU-Ag85A), are transiently protected against pathology caused by intradermal challenge with MU. Building upon this principle, we have generated quality-controlled, live-recombinant strains of BCG and M. smegmatis which express the immunodominant MU Ag85A. Priming with rBCG MU-Ag85A followed by an M. smegmatis MU-Ag85A boost strongly induced murine antigen-specific CD4+ T cells and elicited functional IFNγ-producing splenocytes which recognized MU-Ag85A peptide and whole M. ulcerans better than a BCG prime-boost vaccination. Strikingly, mice vaccinated with a single subcutaneous dose of BCG MU-Ag85A or prime-boost displayed significantly enhanced survival, reduced tissue pathology, and lower bacterial load compared to mice vaccinated with BCG. Importantly, this level of superior protection against experimental Buruli ulcer compared to BCG has not previously been achieved. These results suggest that use of BCG as a recombinant vehicle expressing MU antigens represents an effective Buruli ulcer vaccine strategy and warrants further antigen discovery to improve vaccine efficacy. PMID:26393347

  14. Polyneuritis following BCG re-vaccination

    OpenAIRE

    Katznelson, D; Gross, S.; Sack, J

    1982-01-01

    A 12-year-old healthy, tuberculin negative boy was re-vaccinated with BCG. Nine days later symmetrical polyneuritis developed in all extremities. The tuberculin test was now strongly positive. It is suggested that the polyneuritis was due to a hypersensitivity reaction resulting from the BCG re-vaccination.

  15. BCG induced granulomatous prostatitis ; a case report

    International Nuclear Information System (INIS)

    Granulomatous prostatitis was relatively uncommon until the introduction of intravesical BCG for the treament of bladder cancer. Since that time, there has been an increase in the number of cases of granulomatous prostatitis, but the domestic literature contains no report. We recently encountered a classic case of BCG induced granulomatous prostatitis and describe this case, including its radiologic findings. (author)=20

  16. Immunotherapy with irradiated tumour cells and BCG in experimental osteosarcoma

    International Nuclear Information System (INIS)

    The effects of immunotherapy with irradiated tumour cells and BCG were studied in a non-metastasizing variety of the Dunn osteosarcoma transplantable in mice. Experimental animals which had been preimmunized with three injections of 0.7 to 1.4 x 106 irradiated tumour cells each 1 to 3 weeks before administration of 1 x 106 living tumour cells, showed a tumour incidence of 23 per cent. This was significantly (P<0.005) lower than the 92 per cent tumour incidence in the control animals. Non-specific immunotherapy with BCG given subcutaneously at a dose of 1.0 mg of dry-weight bacterial mass three times at 3-weeks intervals was found to have no protective effect against the osteosarcoma. The tumour incidence was 90 per cent for BCG-treated and 94 per cent for control animals. The osteosarcomas were studied light and electron microscopically and also with regard to the histochemical alkaline phosphatase activity. No structural difference was found between the tumours of the various groups. The demonstrated immunotherapeutic response is in contrast o the low degree of immunogenicity of the osteosarcoma, which we will report elsewhere. (author)

  17. Susceptibility of Mycobacterium bovis BCG Vaccine Strains to Antituberculous Antibiotics▿

    OpenAIRE

    Ritz, Nicole; Tebruegge, Marc; Connell, Tom G.; Sievers, Aina; Robins-Browne, Roy; Curtis, Nigel

    2008-01-01

    Mycobacterium bovis BCG is one of the most commonly administered vaccines. Complications, including disseminated BCG disease, are rare but increasingly reported in immunodeficient children. There is growing recognition of the importance of differences between BCG vaccine strains. We determined the susceptibilities of five genetically distinct BCG vaccine strains to 12 antituberculous drugs.

  18. Repeated Aerosolized-Boosting with Gamma-Irradiated Mycobacterium bovis BCG Confers Improved Pulmonary Protection against the Hypervirulent Mycobacterium tuberculosis Strain HN878 in Mice.

    Science.gov (United States)

    Cha, Seung Bin; Kim, Woo Sik; Kim, Jong-Seok; Kim, Hongmin; Kwon, Kee Woong; Han, Seung Jung; Eum, Seok-Yong; Cho, Sang-Nae; Shin, Sung Jae

    2015-01-01

    Mycobacterium bovis bacillus Calmette-Guerin (BCG), the only licensed vaccine, shows limited protection efficacy against pulmonary tuberculosis (TB), particularly hypervirulent Mycobacterium tuberculosis (Mtb) strains, suggesting that a logistical and practical vaccination strategy is urgently required. Boosting the BCG-induced immunity may offer a potentially advantageous strategy for advancing TB vaccine development, instead of replacing BCG completely. Despite the improved protection of the airway immunization by using live BCG, the use of live BCG as an airway boosting agent may evoke safety concerns. Here, we analyzed the protective efficacy of γ-irradiated BCG as a BCG-prime boosting agent for airway immunization against a hypervirulent clinical strain challenge with Mycobacterium tuberculosis HN878 in a mouse TB model. After the aerosol challenge with the HN878 strain, the mice vaccinated with BCG via the parenteral route exhibited only mild and transient protection, whereas BCG vaccination followed by multiple aerosolized boosting with γ-irradiated BCG efficiently maintained long-lasting control of Mtb in terms of bacterial reduction and pathological findings. Further immunological investigation revealed that this approach resulted in a significant increase in the cellular responses in terms of a robust expansion of antigen (PPD and Ag85A)-specific CD4+ T cells concomitantly producing IFN-γ, TNF-α, and IL-2, as well as a high level of IFN-γ-producing recall response via both the local and systemic immune systems upon further boosting. Collectively, aerosolized boosting of γ-irradiated BCG is able to elicit strong Th1-biased immune responses and confer enhanced protection against a hypervirulent Mycobacterium tuberculosis HN878 infection in a boosting number-dependent manner. PMID:26509812

  19. Mitsuda's reactions: induced by BCG in the normal Rhesus ("Macacca mulatta"

    Directory of Open Access Journals (Sweden)

    M. J. Pereira Filho

    1955-12-01

    the repetition of the tests, even though the intensity of the reaction always remains the same. This precocious reaction (Fernandez type occurs both shortly and long time after the application of the BCG. Its precocity depends not of the antigen only because the first Mitsuda's reaction after the BCG application occurs after some time and seems not influenced by the control lepromin test effected on the Rhesus before the BCG. 5 On the control group, the animals which received a.a.f. bacilli suspensions (Mycobacterium sp.; M. avium, and M. smegmatis, did not show reverseals of the Mitsuda's reaction. Two Rhesus, however, which received dead BCG (120ºC autoclave 1 hour, one intradermically (0.006 g and the other orally (1.2 g, did both present reversals of the Mitsuda's reaction, with weak positivity (+. In all animals of the control-group, the allergic reactions were found negative. 6 Strong local inflammatory reactions were observed in the Rhesus that had received living BCG by intradermal via, and in the one submitted to multipunctures, there occurred the formation of a large caseous abcess. 7 The allergic tuberculinic and infratuberculinic reactions appeared dissociated from the Mitsuda's reactions: sometimes they are more precocious, occurring before of the lepromin test; on other occasions they disappear, when the Mitsuda's reactions still persist; and finally, they may be absent, when the latter occur, especially after the oral application of the BCG. 8 In Rhesus which received BCG by testicular and peritonela via, in the infratuberculinic test (0.1 ml of total BCG extract, besides the classic answer, which occurs between 48 and 96 hours, one could observe a delayed answer (15 to 20 days, represented by a non-erythematous nodule, which persists for 11-14 days.

  20. The BCGΔBCG1419c strain, which produces more pellicle in vitro, improves control of chronic tuberculosis in vivo.

    Science.gov (United States)

    Pedroza-Roldán, César; Guapillo, Carolina; Barrios-Payán, Jorge; Mata-Espinosa, Dulce; Aceves-Sánchez, Michel de Jesús; Marquina-Castillo, Brenda; Hernández-Pando, Rogelio; Flores-Valdez, Mario Alberto

    2016-09-14

    Mycobacterium tuberculosis (Mtb) has been a threat to humans since ancient times, and it is the main causative agent of tuberculosis (TB). Until today, the only licensed vaccine against Mtb is the live attenuated M. bovis Bacillus Calmette-Guérin (BCG), which has variable levels of protection against the pulmonary form of infection. The quest for a new vaccine is a priority given the rise of multidrug-resistant Mtb around the world, as well as the tremendous burden imposed by latent TB. The objective of this study was to evaluate the immunogenicity and capacity of protection of a modified BCG strain (BCGΔBCG1419c) lacking the c-di-GMP phosphodiesterase gene BCG1419c, in diverse mice models. In a previous report, we have shown that BCGΔBCG1419c was capable of increasing biofilm production and after intravenous infection of immunocompetent mice; this strain persisted longer in lungs than parental BCG Pasteur. This led us to hypothesize that BCGΔBCG1419c might therefore possess some advantage as vaccine candidate. Our results in this report indicate that compared to conventional BCG, vaccination with BCGΔBCG1419c induced a better activation of specific T-lymphocytes population, was equally effective in preventing weight loss despite being used at lower dose, reduced tissue damage (pneumonic scores), increased local IFNγ(+) T cells, and diminished bacterial burden in lungs of BALB/c mice infected intratracheally with high dose Mtb H37Rv to induce progressive TB. Moreover, vaccination with BCGΔBCG1419c improved resistance to reactivation after immunosuppression induced by corticosterone in a murine model of chronic infection similar to latent TB. Furthermore, despite showing increased persistence in immunocompetent mice, BCGΔBCG1419c was as attenuated as parental BCG in nude mice. To our knowledge, this is the first demonstration that a modified BCG vaccine candidate with increased pellicle/biofilm production has the capacity to protect against Mtb challenge in

  1. Effect of Experimental Parameters on Alginate/Chitosan Microparticles for BCG Encapsulation.

    Science.gov (United States)

    Caetano, Liliana A; Almeida, António J; Gonçalves, Lídia M D

    2016-01-01

    The aim of the present study was to develop novel Mycobacterium bovis bacille Calmette-Guérin (BCG)-loaded polymeric microparticles with optimized particle surface characteristics and biocompatibility, so that whole live attenuated bacteria could be further used for pre-exposure vaccination against Mycobacterium tuberculosis by the intranasal route. BCG was encapsulated in chitosan and alginate microparticles through three different polyionic complexation methods by high speed stirring. For comparison purposes, similar formulations were prepared with high shear homogenization and sonication. Additional optimization studies were conducted with polymers of different quality specifications in a wide range of pH values, and with three different cryoprotectors. Particle morphology, size distribution, encapsulation efficiency, surface charge, physicochemical properties and biocompatibility were assessed. Particles exhibited a micrometer size and a spherical morphology. Chitosan addition to BCG shifted the bacilli surface charge from negative zeta potential values to strongly positive ones. Chitosan of low molecular weight produced particle suspensions of lower size distribution and higher stability, allowing efficient BCG encapsulation and biocompatibility. Particle formulation consistency was improved when the availability of functional groups from alginate and chitosan was close to stoichiometric proportion. Thus, the herein described microparticulate system constitutes a promising strategy to deliver BCG vaccine by the intranasal route. PMID:27187418

  2. Immunological evaluation of a component isolated from Mycobacterium bovis BCG with a monoclonal antibody to M. bovis BCG.

    OpenAIRE

    Minden, P; Kelleher, P J; Freed, J. H.; Nielsen, L. D.; Brennan, P J; McPheron, L; McClatchy, J K

    1984-01-01

    A component of Mycobacterium bovis BCG referred to as BCG-a was isolated through the combined use of monoclonal antibody directed to BCG and affinity chromatography. Analysis of BCG-a by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a single prominent band with a molecular weight of ca. 10,000. Structural characterization of BCG-a consisting of amino acid composition and amino-terminal sequence determination was carried out. The intact BCG-a antigen was bound by neither t...

  3. Proteomic profile of culture filtrate from the Brazilian vaccine strain Mycobacterium bovis BCG Moreau compared to M. bovis BCG Pasteur

    Directory of Open Access Journals (Sweden)

    Degrave Wim M

    2011-04-01

    Full Text Available Abstract Background Bacille Calmette-Guerin (BCG is currently the only available vaccine against tuberculosis (TB and comprises a heterogeneous family of sub-strains with genotypic and phenotypic differences. The World Health Organization (WHO affirms that the characterization of BCG sub-strains, both on genomic and proteomic levels, is crucial for a better comprehension of the vaccine. In addition, these studies can contribute in the development of a more efficient vaccine against TB. Here, we combine two-dimensional electrophoresis (2DE and mass spectrometry to analyse the proteomic profile of culture filtrate proteins (CFPs from M. bovis BCG Moreau, the Brazilian vaccine strain, comparing it to that of BCG Pasteur. CFPs are considered of great importance given their dominant immunogenicity and role in pathogenesis, being available for interaction with host cells since early infection. Results The 2DE proteomic map of M. bovis BCG Moreau CFPs in the pH range 3 - 8 allowed the identification of 158 spots corresponding to 101 different proteins, identified by MS/MS. Comparison to BCG Pasteur highlights the great similarity between these BCG strains. However, quantitative analysis shows a higher expression of immunogenic proteins such as Rv1860 (BCG1896, Apa, Rv1926c (BCG1965c, Mpb63 and Rv1886c (BCG1923c, Ag85B in BCG Moreau when compared to BCG Pasteur, while some heat shock proteins, such as Rv0440 (BCG0479, GroEL2 and Rv0350 (BCG0389, DnaK, show the opposite pattern. Conclusions Here we report the detailed 2DE profile of CFPs from M. bovis BCG Moreau and its comparison to BCG Pasteur, identifying differences that may provide relevant information on vaccine efficacy. These findings contribute to the detailed characterization of the Brazilian vaccine strain against TB, revealing aspects that may lead to a better understanding of the factors leading to BCG's variable protective efficacy against TB.

  4. Effectiveness of BCG vaccination to aged mice

    Directory of Open Access Journals (Sweden)

    Ito Tsukasa

    2010-09-01

    Full Text Available Abstract Background The tuberculosis (TB still increases in the number of new cases, which is estimated to approach 10 million in 2010. The number of aged people has been growing all over the world. Ageing is one of risk factors in tuberculosis because of decreased immune responses in aged people. Mycobacterium bovis Bacillus Calmette Guérin (BCG is a sole vaccine currently used for TB, however, the efficacy of BCG in adults is still a matter of debate. Emerging the multidrug resistant Mycobacterium tuberculosis (MDR-TB make us to see the importance of vaccination against TB in new light. In this study, we evaluated the efficacy of BCG vaccination in aged mice. Results The Th1 responses, interferon-γ production and interleukin 2, in BCG inoculated aged mice (24-month-old were comparable to those of young mice (4- to 6-week-old. The protection activity of BCG in aged mice against Mycobacterium tuberculosis H37Rv was also the same as young mice. Conclusion These findings suggest that vaccination in aged generation is still effective for protection against tuberculosis.

  5. BCG-itis — case report, review of the literature

    OpenAIRE

    Brzezinski, Piotr

    2013-01-01

    Tuberculosis still remains a huge global health problem. Control of tuberculosis expansionis very difficult. It requires the long-term use of anti-mycobacterial drugs. The BacilleCalmette-Guérin (BCG) vaccination protects against tuberculosis-related meningitis and disseminatedtuberculosis. Although vaccination with BCG is considered safe, adverse regional(BCG-itis) and disseminated (BCG-osis) diseases preferentially occur in the immunocompromisedhost. The infection with human immunodeficienc...

  6. Doit-on encore recommander le vaccin BCG?

    OpenAIRE

    Collette, Georges; Bourhaba, Maryam; Moutschen, Michel

    2006-01-01

    The BCG vaccine has demonstrated its efficacy to protect young children from severe extrapulmonary forms of tuberculosis. Nevertheless, the immunity induced by the vaccine disappears in adults and cannot be boosted by readministration of BCG. Adverse effects of BCG are rare, but potentially dangerous (i.e. disseminated vaccinal infections) and they justify the fact that BCG should not be administered anymore in Western European countries where the incidence of pediatric tuberculous meningitis...

  7. Evaluation of BCG Vaccine in Excessive Dermal Reactivity Test

    OpenAIRE

    Malik, Neeraj; Kasana, Harit; Sikarwar, Gunjan; Pathania, Lavanyam; Tewari, Shalini; Kiran, Manjula; Soni, G. R.; Singh, Surinder

    2015-01-01

    BCG vaccine has been in use globally to control the tuberculosis since the year 1921 and there has been significant achievement to curtail the disease. The important tests as per pharmacopoeial requirements including count of viable units (CVU) and excessive dermal reactivity (EDR) are required to be performed for ensuring the quality of BCG vaccine. In order to see the trend analysis of EDR of BCG vaccine used in India, a study has been carried out using 35 batches of BCG vaccine manufacture...

  8. Adjuvant immunotherapy with BCG in squamous cell bronchial carcinoma.

    OpenAIRE

    Jansen, H.M.; The, T H; Orie, N G

    1980-01-01

    Fifty-four patients with evidence of locally advanced primary squamous cell bronchial carcinoma (SCC), and three patients with adenocarcinoma (AC) had lung resection to remove all the visible tumour. After operation an randomly chosen group of 20 SCC patients received adjuvant BCG immunostimulation by scarifications (BCG-A). An additional group of 14 SCC patients, and three AC patients received initially intrapleural BCG treatment and subsequently scarifications (BCG-B). A control group of 20...

  9. Non-specific immunity of BCG vaccine: A perspective of BCG immunotherapy

    Directory of Open Access Journals (Sweden)

    Najeeha Talat Iqbal

    2014-01-01

    Full Text Available BCG is a widely used vaccine worldwide for neonates including Pakistan. BCG has more than 90% coverage through the EPI program which was introduced in 1965 in Pakistan. BCG has limited efficacy against the transmissible form of pulmonary tuberculosis in high TB endemic countries. However, BCG vaccination continues in these countries because BCG confers protection against the disseminated form of TB in children. BCG has also shown some protection against leprosy and certain forms of cancers. One reason for such nonspecific protection may be that BCG activates APCs via PAMPS that interacts with TLRs (2, 4 & 8, which initiate the inflammatory cascade thereby recruiting inflammatory cells to the site of infection and providing maturation signals for neutrophils, macrophages and dendritic cells. Such activation may be crucial for restricting the infection at the initial site. Furthermore, activation of the pro-inflammatory cascade also results in expression of adhesion molecules, co-stimulatory molecules as well as MHC class II molecule. MHC class II molecules engage CD4+ cells via the TCR receptor while the adhesion and costimulatory molecules bind to their respective receptors on CD4+ T cells for additional high affinity binding for T cell activation. Although activation of the innate arm may not provide subsequent memory, activation of T cells may introduce a certain level of memory response and therefore, may form a rational basis for BCG immunotherapy. This review, therefore, focuses on the immune activation related to both the innate and adaptive arm of the immune response that has been reported and further explores the utility of BCG immunotherapy related to non TB conditions.

  10. BCG protects toddlers during a tuberculosis outbreak.

    LENUS (Irish Health Repository)

    Gaensbauer, J T

    2009-05-01

    In 2007, an outbreak of tuberculosis occurred in a toddler population attending two child care centres in Cork, Ireland. Of 268 children exposed, 18 were eventually diagnosed with active tuberculosis. We present the initial clinical and radiographic characteristics of the active disease group. Mantoux testing was positive in only 66% of cases. All cases were either pulmonary or involved hilar adenopathy on chest radiograph; there were no cases of disseminated disease or meningitis. 24% of the exposed children had been previously vaccinated with BCG, and no case of active disease was found in this group (p = 0.016), suggesting a profound protective effect of BCG in this population. Our experience provides evidence supporting a protective effect of BCG against pulmonary disease in young children.

  11. The most massive MaxBCG clusters

    Science.gov (United States)

    Murray, Stephen

    2014-09-01

    Great progress on galaxy clusters has been made in the last several years with SZ and optical surveys. Some new puzzles also emerged and one of them is the mismatch between the stacked Planck SZ fluxes and the model expectations for the MaxBCG clusters. While previous studies regarding this puzzle require the calibration of the true mass and the standard pressure template, we bypass the intermediate steps to directly compare the pressure content derived from the X-ray data with the SZ flux, for massive MaxBCG clusters. This proposal requests Chandra data for 3 clusters to complete a sample of 12 most massive MaxBCG clusters observed with either XMM or Chandra. The results will shed light on the mismatch puzzle and constrain the important scaling relations like Y_X - N_200 and Y_X - Y_SZ.

  12. BCG protects against tuberculosis irrespective of HIV status

    DEFF Research Database (Denmark)

    Faurholt-Jepsen, Daniel; Range, Nyagosya; Praygod, George Amani;

    2013-01-01

    While BCG vaccine protects against severe tuberculosis (TB) in children, its effect against adult TB is questionable. Furthermore, it is not known if HIV co-infection modifies the effect of BCG. Among 352 pairs of Tanzanian TB cases and matched controls, the BCG scar was associated with a reduced...

  13. Randomized trial of BCG vaccination at birth to low-birth-weight children

    DEFF Research Database (Denmark)

    Aaby, Peter; Roth, Adam Anders Edvin; Ravn, Henrik;

    2011-01-01

    Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG.......Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG....

  14. Identification of a 25-kilodalton protein of Mycobacterium bovis BCG to distinguish BCG strains from Mycobacterium tuberculosis.

    OpenAIRE

    Kumar, D; Srivastava, B S; N. B. Singh; Srivastava, R.

    1996-01-01

    Mycobacterium bovis BCG vaccine strains were compared with Mycobacterium tuberculosis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A 25-kDa protein observed in the BCG strains was absent in M. tuberculosis. Rabbit antibodies specific to the 25-kDa protein uniquely identified this protein in BCG strains but not in M. tuberculosis. It is suggested that the 25-kDa protein and polyclonal antibodies directed against this antigen can be exploited to distinguish BCG strains from M. ...

  15. Various ultrasonographic manifestations of Bacille Calmette-Guerin (BCG) lymphadenitis in infants after BCG vaccination

    International Nuclear Information System (INIS)

    To evaluate the various ultrasonographic manifestations of BCG lymphadenitis complicated by BCG vaccination in infants. Among a total of 59 patients of BCG lymphadenitis, we retrospectively evaluated the ultrasonographic findings of five patients (seven involved areas), who were operated and confirmed by histopathology. Three cases were male and two were female and the age range is from 3 months to 9 months (mean: 5.5 months). Among five cases two had only a single lesion and three had multiple lesions, and two of those had multiple lesions at 2 separate locations. All five cases had ipsilateral supraclavicular lesions with same BCG vaccination site and two also had ipsilaeteral axillary lesions. Ultrasonography showed enlarged lymph nodes and heterogeneous hypoechoic changes suggesting internal necrosis or suppurative changes in three cases, but 1 had cystic necrotic change with fluid-fluid level and another had conglomerated mass with intermingled hyper and hypoechoic areas, which were initially suspected to be a tumorous conditions but revealed conglomerated lymph nodes on follow-up ultrasonography and MRI. BCG lymphadenitis is usually located adjacent to a BCG vaccination site, but ultrasonography can show single or multiple lymph node enlargement and various manifestations from homogeneous lymphadenitis to cystic abscess changes and even a mass-like appearance, demonstrating that the evaluation of ultrasonography should be done very carefully.

  16. Auxotrophic complementation as a selectable marker for stable expression of foreign antigens in Mycobacterium bovis BCG.

    Science.gov (United States)

    Borsuk, Sibele; Mendum, Tom A; Fagundes, Michel Quevedo; Michelon, Marcelo; Cunha, Cristina Wetzel; McFadden, Johnjoe; Dellagostin, Odir Antônio

    2007-11-01

    Mycobacterium bovis BCG has the potential to be an effective live vector for multivalent vaccines. However, most mycobacterial cloning vectors rely on antibiotic resistance genes as selectable markers, which would be undesirable in any practical vaccine. Here we report the use of auxotrophic complementation as a selectable marker that would be suitable for use in a recombinant vaccine. A BCG auxotrophic for the amino acid leucine was constructed by knocking out the leuD gene by unmarked homologous recombination. Expression of leuD on a plasmid not only allowed complementation, but also acted as a selectable marker. Removal of the kanamycin resistance gene, which remained necessary for plasmid manipulations in Escherichia coli, was accomplished by two different methods: restriction enzyme digestion followed by re-ligation before BCG transformation, or by Cre-loxP in vitro recombination mediated by the bacteriophage P1 Cre Recombinase. Stability of the plasmid was evaluated during in vitro and in vivo growth of the recombinant BCG in comparison to selection by antibiotic resistance. The new system was highly stable even during in vivo growth, as the selective pressure is maintained, whereas the conventional vector was unstable in the absence of selective pressure. This new system will now allow the construction of potential recombinante vaccine strains using stable multicopy plasmid vectors without the inclusion of antibiotic resistance markers. PMID:17888740

  17. The Cyclic Di-GMP Phosphodiesterase Gene Rv1357c/BCG1419c Affects BCG Pellicle Production and In Vivo Maintenance.

    Science.gov (United States)

    Flores-Valdez, Mario Alberto; Aceves-Sánchez, Michel de Jesús; Pedroza-Roldán, César; Vega-Domínguez, Perla Jazmín; Prado-Montes de Oca, Ernesto; Bravo-Madrigal, Jorge; Laval, Françoise; Daffé, Mamadou; Koestler, Ben; Waters, Christopher M

    2015-02-01

    Bacteria living in a surface-attached community that contains a heterogeneous population, coated with an extracellular matrix, and showing drug tolerance (biofilms) are often linked to chronic infections. In mycobacteria, the pellicle mode of growth has been equated to an in vitro biofilm and meets several of the criteria mentioned above, while tuberculosis infection presents a chronic (latent) phase of infection. As mycobacteria lack most genes required to control biofilm production by other microorganisms, we deleted or expressed from the hsp60 strong promoter the only known c-di-GMP phosphodiesterase (PDE) gene in Mycobacterium bovis BCG. We found changes in pellicle production, cellular protein profiles, lipid production, resistance to nitrosative stress and maintenance in lungs and spleens of immunocompetent BALB/mice. Our results show that pellicle production and capacity to remain within the host are linked in BCG. PMID:25865678

  18. Molecular Characterization of Heterologous HIV-1gp120 Gene Expression Disruption in Mycobacterium bovis BCG Host Strain: A Critical Issue for Engineering Mycobacterial Based-Vaccine Vectors

    Directory of Open Access Journals (Sweden)

    Joan Joseph

    2010-01-01

    Full Text Available Mycobacterium bovis Bacillus Calmette-Guérin (BCG as a live vector of recombinant bacterial vaccine is a promising system to be used. In this study, we evaluate the disrupted expression of heterologous HIV-1gp120 gene in BCG Pasteur host strain using replicative vectors pMV261 and pJH222. pJH222 carries a lysine complementing gene in BCG lysine auxotrophs. The HIV-1 gp120 gene expression was regulated by BCG hsp60 promoter (in plasmid pMV261 and Mycobacteria spp. α-antigen promoter (in plasmid pJH222. Among 14 rBCG:HIV-1gp120 (pMV261 colonies screened, 12 showed a partial deletion and two showed a complete deletion. However, deletion was not observed in all 10 rBCG:HIV-1gp120 (pJH222 colonies screened. In this study, we demonstrated that E. coli/Mycobacterial expression vectors bearing a weak promoter and lysine complementing gene in a recombinant lysine auxotroph of BCG could prevent genetic rearrangements and disruption of HIV 1gp120 gene expression, a key issue for engineering Mycobacterial based vaccine vectors.

  19. Descendant of daughter Brazilian BCG Moreau substrain in Poland.

    Science.gov (United States)

    Krysztopa-Grzybowska, Katarzyna; Brzezińska, Sylwia; Augustynowicz-Kopeć, Ewa; Polak, Maciej; Augustynowicz, Ewa; Lutyńska, Anna

    2012-08-10

    In this study we assessed the genomic stability of Mycobacterium bovis BCG Moreau seed lots used in Poland for BCG vaccine production since 1955 by pulsed field gel electrophoresis (PFGE), amplified fragment length polymorphism (AFLP) and random amplification of polymorphic DNA (RAPD). BCG vaccine lots were more closely related the original lot -M. bovis BCG Rio de Janeiro Moreau compared with seeds used before 1980, which is consistent with seed lot distribution recorded in the archives. We confirmed the presence of RD8, RD2, senX3-regX3, RD14, DU2-I, whiB3, trcR, the second copy of IS6110 inserted in the promoter region of phoP, mutation D322G in phoR, ΔRD1, and ΔfadD26-ppsA in M. bovis BCG Moreau used for BCG production in Poland. However, unlike the Rio de Janeiro parent BCG, the BCG Moreau substrain used in Poland does not harbour a deletion in Rv3887c, a region that is involved in the membrane transport protein that is part of the ESX-2 type VII secretion system. Differences in the distribution of BCG Moreau for its subsequent use for manufacturing influenced the microevolution of BCG Moreau used in Brazil and Poland. PMID:22749596

  20. [A case diagnosed with chronic granulomatous disease after disseminated infection following BCG vaccination].

    Science.gov (United States)

    Delibalta, Güler; Seringeç, Murat; Öncül, Oral

    2015-07-01

    BCG (Bacillus Calmette-Guérin) vaccine is a widely used vaccine with the recommendation of World Health Organization to protect children against miliary tuberculosis (TB) and TB meningitis. Severe side effects related to this vaccine mostly manifest in the presence of underlying immunosuppressive disease. In this report, an infant case with unknown chronic granulomatous disease (CGD) who developed disseminated BCG infection after administration of BCG vaccine, was presented. High fever, left axillary lymphadenopathy and hepatosplenomegaly have developed in a 3-month 28-day female infant, without a known health problem, following BCG vaccination. The acid-fast bacilli (ARB) was isolated from the material of excised lymph node cultivated in Löwenstein-Jensen medium, and the isolate was identified as Mycobacterium bovis. Mycobacterium tuberculosis complex DNA was detected in the axillary lymph node sample by polymerase chain reaction. Anti-tuberculous treatment included 20 mg/kg of rifampicin+10 mg/kg of isoniazid+15 mg/kg of ethambutol+30 mg/kg of streptomycin was started. The patient was then further evaluated for immunodeficiency and on the basis of the results of dihydroamine and LAD (lymphocyte adhesion defect) tests, diagnosed as autosomal recessive CGD. Based on the anamnesis, there was no known immunodeficiency history both in the case during neonatal period and her family members. Interferon-gamma therapy, which is recommended for the patients with CGD living in endemic areas, was initiated. Our patient's fever dropped at the 15th day of anti-tuberculosis treatment, and she was discharged on the 35th day and continued to receive treatment at home. The patient was followed up at outpatient clinic and had no additional complaints; her hepatosplenomegaly was back to normal at the third month. As a result, since BCG vaccine is contraindicated in CGD carriers, newborns with a family history of CGD should be immunologically examined and BCG vaccine should be

  1. Asthmatic Children And Immunological Effects Of BCG Vaccine Key words: Asthmatic children, BCG vaccine

    International Nuclear Information System (INIS)

    A TH2 screwed immune response is known to play a crucial role in the pathogenesis of allergy, so, preventing the differentiation of TH cells. The TH2 cells are appeared as a logical therapeutic approach to atopic asthma. The purpose of TH1 study was to determine the possible role of BCG vaccine on asthma and whether a TH1 type immune response elicited by BCG immunization could suppress the allergic sensitization in childhood asthma. Seventy asthmatic patients (50 atopic and 20 non-atopic) and fifty healthy individuals were subjected to TH1 study. Tuberculin test was performed for all groups then subjects with positive tuberculin test were excluded. The BCG vaccine was given for all groups with assessment of TH1 and TH2 cytokine response by measuring total IgE, IL-4 (for TH2 response) and INF-γ (for TH1 response). Significant reduction in IgE and IL-4, and elevation in INF-γ were determined in group I (atopic asthma) following BCG vaccination. There was non-significant change observed in IgE and IL-4 levels of group II while significant reduction in IL-4 and significant increase in INF-γ was observed after BCG vaccine

  2. Rodent malaria: BCG-induced protection and immunosuppression

    International Nuclear Information System (INIS)

    One dose of 107 viable units of Mycobacterium bovis, strain BCG, protected a significant number of Swiss mice from a primary challenge with 104 thoracic sporozoites of Plasmodium berghei. Immunization with irradiated sporozoites induced greater protection than that observed in BCG-treated animals. Mice treated with BCG and surviving a primary sporozoite challenge were not protected from rechallenge, whereas mice immunized with irradiated sporozoites and surviving initial challenge of sporozoites were solidly immune to further challenge. Immunizing mice with BCG and irradiated sporozoites simulataneously resulted in a synergistic effect of increased protection against a primary challenge of sporozoites only if the two immunogens were administered on the same day and if the mice were challenged 1 to 3 days later. Mice given BCG and irradiated sporozoites and surviving a primary challenge of sporozoites were unable to survive rechallenge. BCG given to mice previously immunized with irradiated sporozoites suppressed their protective immunity against sporozoite challenge

  3. [Study on recombinant BCG to prevent infections of intracellular pathogens].

    Science.gov (United States)

    Takeshi, Y

    2000-07-01

    Studies on recombinant BCG (rBCG) which my group carried out so far were reviewed. Recombinant BCG which secreted alpha antigen-fused foreign antigen was constructed and tested for its ability to induce protective immunity. Thus, rBCG secreting merozoite surface protein 1 (MSP1) of Plasmodium yoelii efficiently protected the infection more than recombinant MSP 1 mixed with artificial adjuvant RAS or IFA did. rBCG which secreted excess amounts of antigen 85 complex A inhibited the multiplication of M. leprae in the footpads of mice. rBCG which secreted alpha antigen-fused IL-2 stimulated peritoneal exudate cells of mice resulting in enhancing killing a bladder cancer cell line in vitro. PMID:10979272

  4. Remarks on Boston Consulting Group Method (BCG)

    OpenAIRE

    Jan Mikus; Edward Bieleninik

    2004-01-01

    The situational plan of an enterprise in the market can be determined by means of the BCG method. The analysis consists in graphical presentation of the spatial distribution of the enterprise activity conditions. The presentation is made in two dimensional spaces in which horizontal axis represents the relative participation of the strategic units in the market and vertical axis represents the market growth rate. In such a coordinate system, enterprise activity can be visualized by means of t...

  5. Evolution of cell types and T-cell subsets in the spleens of Mycobacterium bovis BCG-resistant and M. bovis BCG-susceptible strains of mice after infection with M. bovis BCG.

    OpenAIRE

    Denis, M.; Forget, A; Miailhe, A C; Pelletier, M; Skamene, E

    1985-01-01

    In mice, the early host response to intravenous infection with small doses of dispersed Mycobacterium bovis BCG is controlled by the Bcg gene. After infection with a low dose of M. bovis BCG, Lyt-1+ cells were generated in the spleens of BCG-susceptible mice (Bcgs) in parallel with an increase in the proportion of phagocytic cells. Very few changes occurred in the splenic cell types of BCG-resistant mice (Bcgr).

  6. Tuberculin reaction, BCG scar, and lower female mortality

    DEFF Research Database (Denmark)

    Roth, Adam Anders Edvin; Sodemann, Morten; Jensen, Henrik; Poulsen, Anja; Gustafson, Per; Weise, Christian Frederik; Gomes, Justino; Djana, Queba; Jakobsen, Marianne; Garly, May-Lill; Rodrigues, Amabelia; Aaby, Peter

    2006-01-01

    Recent studies have suggested that bacille Calmette-Guérin (BCG) immunization may have a nonspecific beneficial effect on infant survival and that the effect may be more pronounced among girls. In a prospective birth cohort, we examine whether a positive tuberculin skin test and BCG scar in...... response to BCG immunization were related to better overall survival in Guinea-Bissau and, if so, whether the effect was sex-specific....

  7. Genome sequencing and analysis of BCG vaccine strains.

    Directory of Open Access Journals (Sweden)

    Wen Zhang

    Full Text Available BACKGROUND: Although the Bacillus Calmette-Guérin (BCG vaccine against tuberculosis (TB has been available for more than 75 years, one third of the world's population is still infected with Mycobacterium tuberculosis and approximately 2 million people die of TB every year. To reduce this immense TB burden, a clearer understanding of the functional genes underlying the action of BCG and the development of new vaccines are urgently needed. METHODS AND FINDINGS: Comparative genomic analysis of 19 M. tuberculosis complex strains showed that BCG strains underwent repeated human manipulation, had higher region of deletion rates than those of natural M. tuberculosis strains, and lost several essential components such as T-cell epitopes. A total of 188 BCG strain T-cell epitopes were lost to various degrees. The non-virulent BCG Tokyo strain, which has the largest number of T-cell epitopes (359, lost 124. Here we propose that BCG strain protection variability results from different epitopes. This study is the first to present BCG as a model organism for genetics research. BCG strains have a very well-documented history and now detailed genome information. Genome comparison revealed the selection process of BCG strains under human manipulation (1908-1966. CONCLUSIONS: Our results revealed the cause of BCG vaccine strain protection variability at the genome level and supported the hypothesis that the restoration of lost BCG Tokyo epitopes is a useful future vaccine development strategy. Furthermore, these detailed BCG vaccine genome investigation results will be useful in microbial genetics, microbial engineering and other research fields.

  8. Secretion of human interleukin 2 by recombinant Mycobacterium bovis BCG.

    OpenAIRE

    Kong, D.; Kunimoto, D Y

    1995-01-01

    The human interleukin 2 (huIL-2) gene was introduced into Mycobacterium bovis BCG by using the integrative vector pMV306. To express and secrete huIL-2 from BCG, two different plasmids, CI and CII, were made. In CI, the huIL-2-encoding region was under the control of the alpha-antigen promoter of BCG; in CII, the expression of huIL-2 was regulated by the heat shock protein 60 promoter. A signal peptide sequence isolated from the naturally secreted alpha-antigen of BCG was inserted between the...

  9. Differential Effects of Prior Exposure to Environmental Mycobacteria on Vaccination with Mycobacterium bovis BCG or a Recombinant BCG Strain Expressing RD1 Antigens

    OpenAIRE

    Demangel, Caroline; Garnier, Thierry; Rosenkrands, Ida; Cole, Stewart T.

    2005-01-01

    In silico analysis reveals that most protective antigens expressed by the antituberculous vaccine Mycobacterium bovis BCG (BCG) are conserved in M. avium, supporting the hypothesis that exposure to environmental mycobacteria generates cross-reactive immune responses blocking BCG activity. We investigated the impact of sensitization with M. avium, M. scrofulaceum, or M. vaccae on the protective efficacy of a recombinant BCG strain expressing RD1 antigens (BCG::RD1), using a mouse model of expe...

  10. Safety and Immunogenicity of Boosting BCG Vaccinated Subjects with BCG: Comparison with Boosting with a New TB Vaccine, MVA85A

    OpenAIRE

    Whelan, KT; Pathan, AA; Sander, CR; Fletcher, HA; Poulton, I; Alder, NC; Hill, AV; Mcshane, H.

    2009-01-01

    OBJECTIVES To investigate the safety and immunogenicity of a booster BCG vaccination delivered intradermally in healthy, BCG vaccinated subjects and to compare with a previous clinical trial where BCG vaccinated subjects were boosted with a new TB vaccine, MVA85A. DESIGN Phase I open label observational trial, in the UK. Healthy, HIV-negative, BCG vaccinated adults were recruited and vaccinated with BCG. The primary outcome was safety; the secondary outcome was cellular immune responses ...

  11. Presence of mycobacterial L-forms in human blood: Challenge of BCG vaccination.

    Science.gov (United States)

    Markova, Nadya; Slavchev, Georgi; Michailova, Lilia

    2015-01-01

    Possible persistence of bacteria in human blood as cell wall deficient forms (L-forms) represents a top research priority for microbiologists. Application of live BCG vaccine and L-form transformation of vaccine strain may display a new intriguing aspect concerning the opportunity for occurrence of unpredictable colonization inside the human body by unusual microbial life forms. L-form cultures were isolated from 141 blood samples of people previously vaccinated with BCG, none with a history of exposure to tuberculosis. Innovative methodology to access the unusual L-form elements derived from human blood was developed. The methodology outlines the path of transformation of non- cultivable L-form element to cultivable bacteria and their adaptation for growth in vitro. All isolates showed typical L-forms growth features ("fried eggs" colonies and biofilm). Electron microscopy revealed morphology evidencing peculiar characteristics of bacterial L-form population (cell wall deficient polymorphic elements of variable shape and size). Regular detection of acid fast bacteria in smears of isolated blood L-form cultures, led us to start their identification by using specific Mycobactrium spp. genetic tests. Forty five of 97 genetically tested blood cultures provided specific positive signals for mycobacteria, confirmed by at least one of the 3 specific assays (16S rRNA PCR; IS6110 Real Time PCR and spoligotyping). In conclusion, the obtained genetic evidence suggests that these L-forms are of mycobacterial origin. As the investigated people had been vaccinated with BCG, we can assume that the identified mycobacterial L-forms may be produced by persisting live BCG vaccine. PMID:25874947

  12. Invitro immune responses in children following BCG vaccination

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi V

    2006-01-01

    Full Text Available Introduction: There is still no consensus on the efficacy of BCG vaccine in the prevention of tuberculosis. This study therefore addressed the question of the magnitude of immunity afforded by BCG, by studying the effector mechanisms of protection in children. The main objectives were to assess the degree of immunity conferred by BCG vaccine in children and to identify the most immunogenic antigen(s of BCG by conducting in-vitro studies. Materials and methods: Children in the age-group of 1 to 10 years, were categorized: (A normal, and vaccinated with BCG during the first year, n=45, (B normal, without scar and with no evident history of vaccination, n=31: and (C children admitted in the hospital with a confirmed diagnosis of tuberculosis, n=31. Fractions of BCG were obtained by lysis, sonication, separation by gel chromatography, HPLC and confirmed by SDS-PAGE. In lymphoproliferative assays PBMC were cultured and stimulated with either Concanavalin-A or Tuberculin or the fractions of BCG. Stimulation indices (SI in lymphoproliferation, CD4/CD8 cells, levels of Interferon-γ (IFN- γ in the culture supernatants were measured by ELISA. Results: The vaccinated children displayed significantly high (P< 0.05 mean values of SI in LTT, CD4/CD8 cell ratio against the unfractionated, 67kDa fraction and BCG-CF Ags. While 100% of the vaccinated children had positive lymphoproliferation indices to BCG-CF, only 8.3% of the unvaccinated children were positive. Conclusion: Some of the components of BCG induced a strong Thl cell response in children. These immunogenic antigens were present in the whole cell lysate. The use of BCG vaccine for tuberculosis is worthwhile till a new vaccine is developed.

  13. Protection Induced by Simultaneous Subcutaneous and Endobronchial Vaccination with BCG/BCG and BCG/Adenovirus Expressing Antigen 85A against Mycobacterium bovis in Cattle.

    Science.gov (United States)

    Dean, Gillian S; Clifford, Derek; Whelan, Adam O; Tchilian, Elma Z; Beverley, Peter C L; Salguero, Francisco J; Xing, Zhou; Vordermeier, Hans M; Villarreal-Ramos, Bernardo

    2015-01-01

    The incidence of bovine tuberculosis (bTB) in the GB has been increasing since the 1980s. Immunisation, alongside current control measures, has been proposed as a sustainable measure to control bTB. Immunisation with Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been shown to protect against bTB. Furthermore, much experimental data indicates that pulmonary local immunity is important for protection against respiratory infections including Mycobacterium tuberculosis and that pulmonary immunisation is highly effective. Here, we evaluated protection against M. bovis, the main causative agent of bTB, conferred by BCG delivered subcutaneously, endobronchially or by the new strategy of simultaneous immunisation by both routes. We also tested simultaneous subcutaneous immunisation with BCG and endobronchial delivery of a recombinant type 5 adenovirus expressing mycobacterial antigen 85A. There was significantly reduced visible pathology in animals receiving the simultaneous BCG/BCG or BCG/Ad85 treatment compared to naïve controls. Furthermore, there were significantly fewer advanced microscopic granulomata in animals receiving BCG/Ad85A compared to naive controls. Thus, combining local and systemic immunisation limits the development of pathology, which in turn could decrease bTB transmission. PMID:26544594

  14. INTRAVESICAL BCG THERAPY FOR NON-MUSCLE INVASIVE BLADDER CANCER

    OpenAIRE

    K. M. Figurin

    2014-01-01

    The paper considers the state-of-the-art of BCG vaccine treatment for non-muscle invasive bladder cancer. It gives data on the meta-analyses of foreign studies of the efficiency of BCG therapy in this pathology.

  15. Intravesical BCG therapy as cause of miliary pulmonary tuberculosis.

    Science.gov (United States)

    Rosati, Yuri; Fabiani, Andrea; Taccari, Tommaso; Ranaldi, Renzo; Mammana, Gabriele; Tubaldi, Alberto

    2016-03-01

    Immunotherapy with intravesical bacillus Calmette-Guérin (BCG) is considered the most effective adjuvant to endoscopic resection of bladder urothelial carcinoma in the therapeutic management of non-muscle invasive (NMIBC) at intermediate and high risk of recurrence and progression (pTa - pT1 and high-grade carcinoma in situ, CIS). Despite its proven efficacy, this type of treatment can determine local and systemic side effects of moderate or severe gravity, with the histological diagnosis of epithelioid granulomas in different organs, even in the absence of microbiological positivity of BCG. The immunotherapy with BCG is usually well tolerated and the virulence of the attenuated BCG is very low in immuno-competent patients, although only 16% of patients are able to receive all the instillations of the maintenance period (3 years) of treatment provided by the protocols, precisely because of side effects. Minor side effects usually resolve within a few hours or days. They develop in 3-5% of patients and usually consist of local infectious complications. Manifestations of BCG dissemination, such as vascular and ocular complications, are much less common, while BCG-disseminated infections, with granulomatous pneumonia or hepatitis present, are quite rare, representing 0.5-2% of the complications recorded. We present the clinical case of granulomatous lung and possibly liver infection caused by BCG in a patient aged 56 years being treated for several weeks with intravesical BCG for NIMBC pT1 high grade associated with CIS. PMID:26616461

  16. Complete Genome Sequence of Mycobacterium bovis Strain BCG-1 (Russia).

    Science.gov (United States)

    Sotnikova, Evgeniya A; Shitikov, Egor A; Malakhova, Maja V; Kostryukova, Elena S; Ilina, Elena N; Atrasheuskaya, Alena V; Ignatyev, Georgy M; Vinokurova, Nataliya V; Gorbachyov, Vyacheslav Y

    2016-01-01

    Mycobacterium bovisBCG (Bacille Calmette-Guérin) is a vaccine strain used for protection against tuberculosis. Here, we announce the complete genome sequence ofM. bovisstrain BCG-1 (Russia). Extensive use of this strain necessitates the study of its genome stability by comparative analysis. PMID:27034492

  17. INTRAVESICAL BCG THERAPY FOR NON-MUSCLE INVASIVE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    K. M. Figurin

    2014-07-01

    Full Text Available The paper considers the state-of-the-art of BCG vaccine treatment for non-muscle invasive bladder cancer. It gives data on the meta-analyses of foreign studies of the efficiency of BCG therapy in this pathology.

  18. Tuberculin skin reactivity four years after neonatal BCG vaccination.

    OpenAIRE

    Ormerod, L P; Garnett, J M

    1992-01-01

    Two hundred and sixty one of 279 (93.5%) children known to be tuberculin positive shortly after receiving their neonatal BCG vaccination were still tuberculin positive at age 4 years. The results confirm the continuing effectiveness of neonatal BCG at 4 years.

  19. Redirecting neutrophils against bladder cancer cells by BCG and Smac mimetic combination

    OpenAIRE

    Jinesh G, Goodwin; Kamat, Ashish M

    2012-01-01

    Intravesical bacillus Calmette-Guérin (BCG) immunotherapy results in neutrophil recruitment and subsequent secretion of cytokines to eliminate non-muscle invasive bladder cancer cells. However, bladder cancer cells often resist BCG immunotherapy. Thus, understanding the mechanism of action of BCG, and designing appropriate combination therapies might help to overcome BCG resistance and redirect neutrophils against bladder cancer cells.

  20. Natural killer cell cytokine response to M. bovis BCG Is associated with inhibited proliferation, increased apoptosis and ultimate depletion of NKp44(+CD56(bright cells.

    Directory of Open Access Journals (Sweden)

    Damien Portevin

    Full Text Available Mycobacterium bovis BCG, a live attenuated strain of M. bovis initially developed as a vaccine against tuberculosis, is also used as an adjuvant for immunotherapy of cancers and for treatment of parasitic infections. The underlying mechanisms are thought to rely on its immunomodulatory properties including the recruitment of natural killer (NK cells. In that context, we aimed to study the impact of M. bovis BCG on NK cell functions. We looked at cytotoxicity, cytokine production, proliferation and cell survival of purified human NK cells following exposure to single live particles of mycobacteria. We found that M. bovis BCG mediates apoptosis of NK cells only in the context of IL-2 stimulation during which CD56(bright NK cells are releasing IFN-γ in response to mycobacteria. We found that the presence of mycobacteria prevented the IL-2 induced proliferation and surface expression of NKp44 receptor by the CD56(bright population. In summary, we observed that M. bovis BCG is modulating the functions of CD56(bright NK cells to drive this subset to produce IFN-γ before subsequent programmed cell death. Therefore, IFN-γ production by CD56(bright cells constitutes the main effector mechanism of NK cells that would contribute to the benefits observed for M. bovis BCG as an immunotherapeutic agent.

  1. Variable Virulence and Efficacy of BCG Vaccine Strains in Mice and Correlation With Genome Polymorphisms

    OpenAIRE

    Zhang, Lu; Ru, Huan-wei; Chen, Fu-zeng; Jin, Chun-yan; Sun, Rui-feng; Fan, Xiao-Yong; Guo, Ming; Mai, Jun-tao; Xu, Wen-xi; Lin, Qing-xia; LIU Jun

    2016-01-01

    Bacille Calmette–Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the only vaccine available for tuberculosis (TB) control. However, BCG is not an ideal vaccine and has two major limitations: BCG exhibits highly variable effectiveness against the development of TB both in pediatric and adult populations and can cause disseminated BCG disease in immunocompromised individuals. BCG comprises a number of substrains that are genetically distinct. Whether and how these genetic differen...

  2. Gene Expression and Cytokine Profile Correlate With Mycobacterial Growth in a Human BCG Challenge Model

    OpenAIRE

    Matsumiya, Magali; Satti, Iman; Chomka, Agnieszka; Harris, Stephanie A.; Stockdale, Lisa; Meyer, Joel; Helen A. Fletcher; McShane, Helen

    2014-01-01

    Background.  Bacillus Calmette-Guerin (BCG) vaccine is the most widely administered vaccine in the world, yet its mechanism of action remains unclear. We hypothesize that certain immune pathways are associated with reduced mycobacterial growth following BCG challenge in human volunteers. Methods.  We used samples from a mycobacterial challenge in which previously BCG-vaccinated or BCG-naive adults in the United Kingdom were challenged intradermally with a standard dose of BCG. Any remaining B...

  3. Tuberculin reactivity of children vaccinated at different age with BCG vaccines in preschool period

    OpenAIRE

    Sučilienė, Elena

    2010-01-01

    Object of dissertation: The influence of different BCG vaccination schedules on the tuberculin reactivity, BCG scarring, specific serology and allergy. 509 children were included in this research, all of them received BCG vaccination with standard or half dosage as newborns or 3-months old. 3 months after BCG vaccination and at one, two, and six years of age they were tested with tuberculin, and examined for BCG scarring. Anti-tuberculosis antibodies were detected in sera and children were ev...

  4. Hubungan antara Pembentukan Scar Vaksin BCG dan Kejadian Infeksi Tuberkulosis

    Directory of Open Access Journals (Sweden)

    Fajriah Rosandali

    2016-08-01

    Full Text Available AbstrakTuberkulosis adalah penyakit menular yang disebabkan oleh kuman Mycobacterium tuberculosis. Orang dewasa yang menderita tuberkulosis sangat mudah menularkan kuman TB kepada orang disekitarnya terutama pada anak-anak. Salah satu cara pencegahan penyakit tuberkulosis adalah pemberian imunisasi BCG pada saat bayi baru lahir. Scar vaksin BCG dapat terbentuk setelah penyuntikan, kadang Scar tidak terbentuk setelah penyuntikan. Tujuan penelitian ini adalah menentukan hubungan antara pembentukan Scar vaksin BCG dan kejadian infeksi tuberkulosis. Penelitian ini menggunakan desain cross sectional dengan jumlah subjek sebanyak 80 orang. Pengambilan data berupa melakukan pengamatan terhadap Scar pada lengan atas serta wawancara kepada responden dengan menggunakan pedoman wawancara. Kemudian data ditabulasi dalam bentuk persentase dan dianalisis dengan uji chi-square . Hasil penelitian menunjukan bahwa responden yang terbanyak adalah perempuan dan usia yang terbanyak 35-44 tahun. Terdapat hubungan yang bermakna antara pembentukan Scar  vaksin BCG dengan kejadian infeksi tuberkulosis (p < 0,05. Disimpulkan bahwa terdapat pengaruh antara pembentukan Scar vaksin BCG terhadap kejadian infeksi tuberkulosis.Kata kunci: tuberkulosis, vaksin BCG, Scar. AbstractTuberculosis is an infectious disease caused by Mycobacterium tuberculosis with the number of sufferers tend to increase every years. Adults who suffer  tuberculosis is very easy to spread it to around, especially to children. One of the way to prevent tuberculosis is immunization of BCG vaccine which given since infant. The Scar of BCG vaccine can formed after injection or not. The objective of this study was to determine the relation of BCG vaccine Scar formation on  the incidence of tuberculosis infection.This research used a cross sectional design with 80 total subjects. The data was collected by observations of the scar on the upper arm while interviewed  respondents using interview guide

  5. BCG plus levamisole following irradiation of advanced squamous bronchial carcinoma

    International Nuclear Information System (INIS)

    Fifty patients with inoperable squamous cell carcinoma of the bronchus were treated with radical radiotherapy. Afterwards, 16 patients received levamisole on 2 days per week and bacillus calmette guerin (B.C.G.) skin innoculations every two weeks;another 16 received the same dosage of levamisole but B.C.G. every 4 weeks; 18 patients were controls. Survival was better in the first group of patients only during the first two years of study (P = 0.02) but not later: metastases were fewer. Both B.C.G. and levamisole gave little discomfort when the dose was adjusted for each patient

  6. L’utilisation des strat��gies d’apprentissage d’une langue dans un environnement des TICE L’utilisation des stratégies d’apprentissage d’une langue dans un environnement des TICE

    Directory of Open Access Journals (Sweden)

    Janet Atlan

    2000-06-01

    Full Text Available L'étude des différences individuelles qui caractérisent les apprenants s'intègre de plus en plus dans les travaux en didactique des langues. L'utilisation des stratégies d'apprentissage est un type de différences individuelles qui semble être assez sensible à l'environnement pédagogique. Cet article rend compte d'une étude expérimentale entreprise avec des étudiants français en IUT qui avait pour objectif de déterminer si l'utilisation des stratégies d'apprentissage par un apprenant de langues est influencée par la technologie de l'information et de la communication (TIC utilisée pour la présentation d'une tâche d'apprentissage. Le "Strategy Inventory for Language Learning" d'Oxford a été utilisé comme instrument lors de cette étude. L'étude a montré qu'il y a effectivement interaction entre la TIC utilisée et le choix de stratégies effectué par l'apprenant et les résultats permettent de tirer quelques conclusions quant à l'utilité d'un entraînement spécifique à l'utilisation des stratégies d'apprentissage en présence des technologies de l’information et de la communication pour l’enseignement (TICE.The study of the individual differences which characterize learners is becoming more and more common in language learning research, and the use of learning strategies is an instance of individual differences which seems to be rather sensitive to the pedagogical environment. This article reports on an experimental study undertaken with students in a French technical college to determine if the use of learning strategies by a foreign language student is influenced by the technology used to present a language learning task. Oxford's Strategy Inventory for Language Learning was the principal instrument used for this study. The study showed that there was indeed some interaction between the technology used and the choice of learning strategies and the results lead to some interesting considerations on the usefulness

  7. Delaying BCG Vaccination Until 8 Weeks of Age Results in Robust BCG-Specific T-Cell Responses in HIV-Exposed Infants

    OpenAIRE

    Tchakoute, Christophe Toukam; Hesseling, Anneke C.; Kidzeru, Elvis B.; Gamieldien, Hoyam; Passmore, Jo-Ann S.; Jones, Christine E.; Gray, Clive M.; Sodora, Donald L.; Jaspan, Heather B.

    2014-01-01

    Background. BCG vaccination prevents disseminated tuberculosis in children, but it is contraindicated for persons with human immunodeficiency virus (HIV) infection because it can result in severe disease in this population. In tuberculosis-endemic regions, BCG vaccine is administered soon after birth, before in utero and peripartum HIV infection is excluded. We therefore assessed the immunogenicity of BCG vaccine in HIV-exposed infants who received BCG at birth or at 8 weeks of age.

  8. The Abell 85 BCG: a nucleated, core-less galaxy

    CERN Document Server

    Madrid, Juan P

    2016-01-01

    New high-resolution r band imaging of the brightest cluster galaxy (BCG) in Abell 85 (Holm 15A) was obtained using the Gemini Multi Object Spectrograph. These data were taken with the aim of deriving an accurate surface brightness profile of the BCG of Abell 85, in particular its central region. The new Gemini data show clear evidence of a previously unreported nuclear emission that is evident as a distinct light excess in the central kiloparsec of the surface brightness profile. We find that the light profile is never flat nor does it present a downward trend towards the center of the galaxy. That is, the new Gemini data show a different physical reality from the featureless, "evacuated core" recently claimed for the Abell 85 BCG. After trying different models, we find that the surface brightness profile of the BCG of Abell 85 is best fit by a double Sersic model.

  9. The Abell 85 BCG: A Nucleated, Coreless Galaxy

    Science.gov (United States)

    Madrid, Juan P.; Donzelli, Carlos J.

    2016-03-01

    New high-resolution r-band imaging of the brightest cluster galaxy (BCG) in Abell 85 (Holm 15A) was obtained using the Gemini Multi Object Spectrograph. These data were taken with the aim of deriving an accurate surface brightness profile of the BCG of Abell 85, in particular, its central region. The new Gemini data show clear evidence of a previously unreported nuclear emission that is evident as a distinct light excess in the central kiloparsec of the surface brightness profile. We find that the light profile is never flat nor does it present a downward trend toward the center of the galaxy. That is, the new Gemini data show a different physical reality from the featureless, “evacuated core” recently claimed for the Abell 85 BCG. After trying different models, we find that the surface brightness profile of the BCG of Abell 85 is best fit by a double Sérsic model.

  10. Mechanisms of recrudescence of Mycobacterium bovis BCG infection in mice.

    OpenAIRE

    Cox, J H; Knight, B. C.; Ivanyi, J.

    1989-01-01

    The capacity of various immunosuppressive agents to cause a recrudescence of the replication of Mycobacterium bovis BCG in the spleens of chronically infected mice was investigated. The actions of three corticosteroid preparations, cyclosporin A, and anti-T-cell subset monoclonal antibodies were compared. Treatment of mice with hydrocortisone acetate, which depressed the number of splenic lymphocytes and suppressed T-cell responses, most effectively exacerbated the stationary BCG counts, at 4...

  11. Genome Sequencing and Analysis of BCG Vaccine Strains

    OpenAIRE

    Zhang, Wen; Zhang, Yuanyuan; Zheng, Huajun; Pan, Yuanlong; Liu, Haican; Du, Pengcheng; Wan, Li; LIU Jun; Zhu, Baoli; Zhao, Guoping; Chen, Chen; Wan, Kanglin

    2013-01-01

    Background Although the Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis (TB) has been available for more than 75 years, one third of the world's population is still infected with Mycobacterium tuberculosis and approximately 2 million people die of TB every year. To reduce this immense TB burden, a clearer understanding of the functional genes underlying the action of BCG and the development of new vaccines are urgently needed. Methods and Findings Comparative genomic analysis of 1...

  12. SIMULTANEOUS SMALLPOX AND B.C.G. VACCINATION IN INDONESIA

    Directory of Open Access Journals (Sweden)

    Nyoman Kumara Rai

    2012-09-01

    Full Text Available Vaksinasi cacar dan BCG mulai diberikan secara simultan di Jawa dan Bali pada bulan April 1972 vaksinasi cacar diberikan pada lengan kiri dan BCG pada lengan kanan. Secara berangsur-angsur prograi ini kemudian diperluas kedaerah luar Jawa-Bali, sehingga pada akhir tahun 1973 sudah mencakup seluruh Indonesia. Tenaga yang digunakan adalah para juru cacar yang sudah ada dalam rangka proyek pembasmian penyakit cacar yang dimulai tahun 1968, dan terdapat hampir disemua kecamatan diseluru Indonesia. Ide untuk menggabungkan kedua jenis vaksinasi ini yang kebetulan mempunyai target sam (anak2 0 - 14 thn  timbul setelah penderita cacar tidak dilaporkan lagi dibulan September 1971 (ternyata kemudian letusan cacar terakhir adalah dibulan Desember 1971. Sampai saat itu vaksina BCG dilakukan oleh petugas Puskesmas dan tenaga part timer. Ternyata target tidak pernah tercapa hal ini mungkin disebabkan oleh terbatasnya waktu yang tersedia untuk melakukan vaksinasi BCC sehingga para tenaga part timer tsb. hanya mampu mencakup daerah disekitar Puskesmas dan sekolah dasar. Sebelumnya telah diadakan dua trial; yang pertama diadakan di Bandung untuk melihat at tidaknya saling pengaruh mempengaruhi antara kedua jenis vaksin cacar dan BCG bila diberikan pat saat yang bersamaan, sedangkain trial kedua dilakukan untuk menilai kemampuan juru cacar dala melaksanakan vaksinasi BCG serta kesukaran! yang dijumpai dilapangan (masing2 didua kabupaten (Jawa Tengah, Timur dan Yogyakarta. Disamping keuntungan yang diperoleh dari penggabungan kedua jenis vaksinasi ini yakni penghematan tenaga, biaya dan waktu, dijumpai juga beberapa kesukaran antara lain pengumpulan anak2, supply vaksin BCG yang tidak teratur dll. Walaupun demikian, di Jawa dan Bali hasil vaksinasi BCG antara April 1972 sampai dengan April 1973 menunjukkan kenaikan out-put leb dari 4 kali lipat bila dibandingkan dengan out-put sebelum penggabungan, meskipun out-put prin vaksinasi cacar mempunyai tendensi menurun

  13. Disseminated BCG infection in a patient with severe combined immunodeficiency

    International Nuclear Information System (INIS)

    Disseminated mycobacterial infection after bacillus Calmette-Guerin (BCG) accination is a very rare disorder, occurring mostly in patients with immunologic eficiency. We report a case of disseminated BCG infection in a 16-month-old girl with severe combined immunodeficiency. Plain radiographs showed multiple osteolytic lesions in the femora, tibiae, humerus, and phalanges. Abdominal sonography and CT scanning revealed multiple nodules in the spleen, and portocaval lymphadenopathy

  14. Disseminated tuberculoid lesions in infants following BCG vaccination.

    OpenAIRE

    Trevenen, C. L.; Pagtakhan, R. D.

    1982-01-01

    The records of 830 consecutive autopsies at Children's Hospital, Winnipeg revealed that 26 of the 36 infants (34 Canadian Indian, 1 Inuit and 1 Caucasian) given BCG vaccine shortly after birth had tuberculoid granulomas in various sites, including the vaccination site, regional lymph nodes, liver, spleen, lung, bone marrow and salivary gland. Mycobacterium bovis, BCG type, was identified in three of the four cases in which isolation was attempted. The principal causes of death had been sudden...

  15. SIMULTANEOUS BCG AND SMALLPOX VACCINATION ON NEWBORN INFANTS

    Directory of Open Access Journals (Sweden)

    Abdul Rivai

    2012-09-01

    Full Text Available Telah dikemukakan anggapan-anggapan yang terdapat dewasa ini tentang vaksinasi BCG dan cacar secara simultan. Telah dilakukan vaksinasi BCG dan cacar secara simultan pada 729 neonati dengan freeze dried Smallpox vaccine buatan dari Bio Farma dan freeze dried BCG vaccine Tokyo. Pencacaran dilakukan secara multiple puncture dan bifurcated needle dengan suntikan BCG dengan jarum dan spuit khusus intracutan dengan dosis 0,1 ml. Tuberkulin test dilakukan dengan PPD dari Kopenhagen dengan kekuatan 2 TU 9 minggu setelah vaksinasi. Dari 741 bayi yang diikut sertakan dalam survey, 12 menolak, 3 bayi tidak dapat dilakukan pemeriksaan pertama, 35 bayi belum diperiksa, pemeriksaan pertama telah dilakukan pada 691 bayi. Dari 406 bayi yang seharusnya sudah diperiksa untuk pemeriksaan kedua, 23 dapat dilakukan karena tidak dapat dijumpai atau meninggal. Telah dikemukakan bahwa pencatatan alamat yang jelas dan lengkap serta kesungguhan dalam melakukan home visits sangat penting untuk berhasilnya penyelidikan semacam ini. Dari hasil-hasil yang didapatkan sampai sekarang telah dapat diambil kesimpulan sementara, bahwa vaksinasi BCG dan cacar secara simultan memberikan hasil yang memuaskan, juga bila dibandingkan dengan hasil-hasil penyelidikan diluar negeri take pada pencacaran 99.4 percent, test tuberkulin dengan PPD 2 TU 9 minggu setelah vaksinasi memberikan indurasi lebih dari 5 mm pada 99.75 percent dan tidak menimbulkan komplikasi-komplikasi. Pelaksanaan vaksinasi BCG dan cacar dapat dilakukan oleh tenaga paramedis yang telah mendapat latihan khusus dan diawasi oleh dokter yang kompeten. Dianjurkan untuk melakukan follow up pada bayi-bayi yang diikut sertakan dalam survey ini.

  16. Manipulation of BCG vaccine: a double-edged sword.

    Science.gov (United States)

    Singh, V K; Srivastava, R; Srivastava, B S

    2016-04-01

    Mycobacterium bovis Bacillus Calmette-Guérin (BCG), an attenuated vaccine derived from M. bovis, is the only licensed vaccine against tuberculosis (TB). Despite its protection against TB in children, the protective efficacy in pulmonary TB is variable in adolescents and adults. In spite of the current knowledge of molecular biology, immunology and cell biology, infectious diseases such as TB and HIV/AIDS are still challenges for the scientific community. Genetic manipulation facilitates the construction of recombinant BCG (rBCG) vaccine that can be used as a highly immunogenic vaccine against TB with an improved safety profile, but, still, the manipulation of BCG vaccine to improve efficacy should be carefully considered, as it can bring in both favourable and unfavourable effects. The purpose of this review is not to comprehensively review the interaction between microorganisms and host cells in order to use rBCG expressing M. tuberculosis (Mtb) immunodominant antigens that are available in the public domain, but, rather, to also discuss the limitations of rBCG vaccine, expressing heterologous antigens, during manipulation that pave the way for a promising new vaccine approach. PMID:26810060

  17. Recombinant BCG: Innovations on an Old Vaccine. Scope of BCG Strains and Strategies to Improve Long-Lasting Memory

    OpenAIRE

    da Costa, Adeliane Castro; Nogueira, Sarah Veloso; Kipnis, André; Junqueira-Kipnis, Ana Paula

    2014-01-01

    Bacille Calmette–Guérin (BCG), an attenuated vaccine derived from Mycobacterium bovis, is the current vaccine of choice against tuberculosis (TB). Despite its protection against active TB in children, BCG has failed to protect adults against TB infection and active disease development, especially in developing countries where the disease is endemic. Currently, there is a significant effort toward the development of a new TB vaccine. This review article aims to address publications on recombin...

  18. Proteomic profile of culture filtrate from the Brazilian vaccine strain Mycobacterium bovis BCG Moreau compared to M. bovis BCG Pasteur

    OpenAIRE

    Degrave Wim M; Castello-Branco Luiz RR; da Silva Renata F; Pereira Melissa P; Gomes Leonardo HF; Correa Paloma R; Kalume Dario E; Berrêdo-Pinho Marcia; Mendonça-Lima Leila

    2011-01-01

    Abstract Background Bacille Calmette-Guerin (BCG) is currently the only available vaccine against tuberculosis (TB) and comprises a heterogeneous family of sub-strains with genotypic and phenotypic differences. The World Health Organization (WHO) affirms that the characterization of BCG sub-strains, both on genomic and proteomic levels, is crucial for a better comprehension of the vaccine. In addition, these studies can contribute in the development of a more efficient vaccine against TB. Her...

  19. The Current Status of BCG Vaccination in Young Children in South Korea

    OpenAIRE

    Lee, Hyejon; Dockrell, Hazel M.; Kim, Deok Ryun; FLOYD, Sian; Oh, Sue Yeon; Lee, Jin Bum; Kim, Hee Jin

    2012-01-01

    Background Delivery of Bacille Calmette-Guréin (BCG) Tokyo vaccine, with the multipuncture device, has been much preferred over BCG Pasteur, with the intradermal method, possibly due to the easier manner of administration, a desire to avoid any trouble with scars, as well as side effects and higher profits to providers in South Korea. Methods To determine BCG scar status in 0~6 year old children vaccinated with two BCG vaccines (Pasteur BCG vaccine with intradermal method and BCG Tokyo vaccin...

  20. The establishment of sub-strain specific WHO Reference Reagents for BCG vaccine

    OpenAIRE

    Dagg, Belinda; Hockley, Jason; Rigsby, Peter; Ho, Mei M.

    2014-01-01

    As the latest addition to the sub-strain specific WHO Reference Reagents of BCG vaccine, an international collaborative study was completed to evaluate the suitability of a candidate BCG Moreau-RJ sub-strain as a WHO Reference Reagent of BCG vaccine. This follows the recent replacement of the WHO 1st International Reference Preparation for BCG vaccine, by three sub-strain specific WHO Reference Reagents of BCG vaccine (Danish 1331, Tokyo 172-1 and Russian BCG-I) in order to complete the cover...

  1. BCG vaccination scar associated with better childhood survival in Guinea-Bissau

    DEFF Research Database (Denmark)

    Roth, Adam Anders Edvin; Gustafson, Per; Nhaga, Alexandro;

    2005-01-01

    Recent studies have suggested that Bacille Calmette-Guerin (BCG) vaccination may have a non-specific beneficial effect on infant survival and that a BCG scar may be associated with lower child mortality. No study has previously examined the influence of BCG vaccination on cause of death.......Recent studies have suggested that Bacille Calmette-Guerin (BCG) vaccination may have a non-specific beneficial effect on infant survival and that a BCG scar may be associated with lower child mortality. No study has previously examined the influence of BCG vaccination on cause of death....

  2. Persistence of the immune response induced by BCG vaccination

    Directory of Open Access Journals (Sweden)

    Blitz Rose

    2008-01-01

    Full Text Available Abstract Background Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. Methods A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-γ response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD in a whole blood assay before, 3 months, 12 months (n = 148 and 3 years (n = 19 after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16. Results A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13% failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13% or 3 (3/19; 16% years. IFN-γ response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81% made a detectable IFN-γ response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38% matched unvaccinated controls (p = 0.012; teenagers vaccinated in infancy were 19 times more likely to make an IFN-γ response of > 500 pg/ml than unvaccinated teenagers. Conclusion BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the

  3. Les TICE pour la production écrite et la traduction de l'italien vers le français : le cas de la SSLMIT de Forlì

    OpenAIRE

    Hamon, Yannick

    2013-01-01

    Les recherches relatives à l'utilisation des TICE se concentrent fréquemment soit sur la dimension cognitive, sur la dimension linguistique ou sur la dimension culturelle. Le plus souvent, les recherches empiriques se proposent d'évaluer les effets directs des TICE sur les performances langagières des apprenants. En outre, les recherches, surtout en psychologie cognitive, sont le plus souvent effectuées en laboratoire. C'est pourquoi le travail présenté dans cette thèse se propose d'inscrire ...

  4. Apprentissage des progiciels et utilisation des TICE pour l'enseignement de la Physique Chimie - Cas de la formation initiale des enseignants de Physique Chimie à l'ENS d'Antananarivo -

    OpenAIRE

    Ratompomalala, Harinosy Hanitriniala

    2011-01-01

    Cet article fait partie d'une thèse dont la problématique est : comment former les enseignants de Physique chimie pour qu'ils puissent utiliser les TICE dans leurs activités professionnelles en classe. Il étudie le cas des futurs professeurs de Physique Chimie de l'ENS d'Antananarivo, qui bénéficient d'une formation en informatique depuis 2008. Une analyse longitudinale de quelques promotions permet d'établir un lien entre cette formation aux progiciels et l'utilisation des TICE par les étudi...

  5. Immunogenicity and Protective Efficacy of a Novel Recombinant BCG Strain Overexpressing Antigens Ag85A and Ag85B

    OpenAIRE

    Chun Wang; Ruiling Fu; Xionglin Fan; Chunwei Shi; Jia Lu; Xindong Teng; Lingxia Chen; Kun Tan; Zhenhua Chen

    2012-01-01

    Recombinant Bacillus Calmette-Guérin (rBCG) strain is the promising vaccine candidate for tuberculosis (TB) prevention, which aims at providing more enduring and enhanced protection than the parental BCG vaccine. In this study, three rBCG strains overexpressing immunodominant antigens Ag85B (rBCG::85B), Ag85A (rBCG::85A), or both (rBCG::AB) of Mycobacterium tuberculosis were constructed, respectively. rBCG strains showed higher level of overexpression of Ag85A and/or Ag85B proteins than BCG c...

  6. Comparative Proteomic Profiling of Mycobacterium bovis and BCG Vaccine Strains

    KAUST Repository

    Gao, Ge

    2013-09-01

    BCG is the only licensed human vaccine currently available against TB. Derived from a virulent strain of M. bovis, the vaccine was thought to have struck a balance between reduced virulence and preserved immunogenicity. Nowadays, BCG vaccine strains used in different countries and vaccination programs show clear variations in their genomes and immune protective properties. The aim of this study was to characterize the proteomic profile on Mycobacterium bovis and five BCG strains Pasteur, Tokyo, Danish, Phipps and Birkhaug by Tandem Mass Tag® (TMT®)-labeling quantitative proteomic approach. In total, 420 proteins were identified and 377 of them were quantitated for their relative abundance. We reported the number and relationship of differential expressed proteins in BCG strains compared to M. bovis and investigated their functions by bioinformatics analysis. Several interesting up-regulated and down-regulated protein targets were found. The identified proteins and their quantitative expression profiles provide a basis for further understanding of the cellular biology of M. bovis and BCG vaccine strains, and hopefully would assist in the design of better anti-TB vaccine and drugs.

  7. Ultraviolet susceptibility of BCG and virulent tubercle bacilli

    International Nuclear Information System (INIS)

    To test the effectiveness of irradiating the upper air of a room with ultraviolet light at reducing the concentration of airborne tubercle bacilli, the susceptibility to the germicidal effects of ultraviolet light, Z, was determined for various mycobacteria. Virulent tubercle bacilli and bacille Calmette-Guerin (BCG) were susceptible to ultraviolet radiation, whereas Mycobacterium phlei had 10 times their resistance (Z, approximately one-tenth that for M. tuberculosis). The effectiveness against BCG of upper air ultraviolet irradiation in a room was tested directly by nebulizing BCG into the air of the room and monitoring its rate of disappearance. With one 17-watt fixture operating, the rate of disappearance increased 6-fold; with 2 fixtures operating (46 watts total), the rate of disappearance increased 9-fold. This implies that under steady-state conditions, the concentrations of airborne organisms with ultraviolet light(s) on would have been one-sixth and one-ninth, respectively. The increase in rate of decay of the airborne organism using 1 fixture was equivalent to 10 air changes per hour, whereas that using 2 fixtures was approximately 25 air changes per hour (range: 18 to 33 air changes per hour). These increments are less than those reported previously for Serratia marcescens, because the Z value for BCG is approximately one-seventh that for serratia. These findings with BCG are believed to be directly applicable to virulent tubercle bacilli

  8. BCG vaccination reduces risk of tuberculosis infection in vaccinated badgers and unvaccinated badger cubs.

    Directory of Open Access Journals (Sweden)

    Stephen P Carter

    Full Text Available Wildlife is a global source of endemic and emerging infectious diseases. The control of tuberculosis (TB in cattle in Britain and Ireland is hindered by persistent infection in wild badgers (Meles meles. Vaccination with Bacillus Calmette-Guérin (BCG has been shown to reduce the severity and progression of experimentally induced TB in captive badgers. Analysis of data from a four-year clinical field study, conducted at the social group level, suggested a similar, direct protective effect of BCG in a wild badger population. Here we present new evidence from the same study identifying both a direct beneficial effect of vaccination in individual badgers and an indirect protective effect in unvaccinated cubs. We show that intramuscular injection of BCG reduced by 76% (Odds ratio = 0.24, 95% confidence interval (CI 0.11-0.52 the risk of free-living vaccinated individuals testing positive to a diagnostic test combination to detect progressive infection. A more sensitive panel of tests for the detection of infection per se identified a reduction of 54% (Odds ratio = 0.46, 95% CI 0.26-0.88 in the risk of a positive result following vaccination. In addition, we show the risk of unvaccinated badger cubs, but not adults, testing positive to an even more sensitive panel of diagnostic tests decreased significantly as the proportion of vaccinated individuals in their social group increased (Odds ratio = 0.08, 95% CI 0.01-0.76; P = 0.03. When more than a third of their social group had been vaccinated, the risk to unvaccinated cubs was reduced by 79% (Odds ratio = 0.21, 95% CI 0.05-0.81; P = 0.02.

  9. BCG-induced pneumonitis with lymphocytic pleurisy in the absence of elevated KL-6

    OpenAIRE

    Tobiume, Makoto; Shinohara, Tsutomu; Kuno, Takahira; Mukai, Shinji; Naruse, Keishi; Hatakeyama, Nobuo; OGUSHI, FUMITAKA

    2014-01-01

    Background Pneumonitis is a rare complication of bacillus Calmette-Guerin (BCG) immunotherapy seen in patients with urothelial cancer following the repeated administration of BCG. However, no case of BCG-induced pleurisy has been reported. Case presentation We here report the first case of pneumonitis with lymphocytic pleurisy following bacillus Calmette-Guerin (BCG) immunotherapy. Although marked T helper cell alveolitis was found by bronchoalveolar lavage and transbronchial biopsies, no aci...

  10. Comparison of immune responses of mice immunized with five different Mycobacterium bovis BCG vaccine strains.

    OpenAIRE

    Lagranderie, M R; Balazuc, A M; Deriaud, E; Leclerc, C D; Gheorghiu, M

    1996-01-01

    Among the various parameters which may contribute to Mycobacterium bovis BCG vaccination efficiency, the choice of the vaccine strain may play an important role. In the present study, we therefore compared the immunogenicity of five different BCG strains that are commonly used for BCG vaccine production (Glaxo 1077, Japanese 172, Pasteur 1173P2, Prague, and Russian strains). The comparison of the growth capacity of these BCG strains in BALB/c and C3H mice demonstrated that a great difference ...

  11. Novel genome polymorphisms in BCG vaccine strains and impact on efficacy

    OpenAIRE

    Gao George; Alexander David C; Yu Xuping; Wu Zuowei; Tran Vanessa; Leung Andrea S; Zhu Baoli; Liu Jun

    2008-01-01

    Abstract Bacille Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis currently used as a vaccine against tuberculosis. Global distribution and propagation of BCG has contributed to the in vitro evolution of the vaccine strain and is thought to partially account for the different outcomes of BCG vaccine trials. Previous efforts by several molecular techniques effectively identified large sequence polymorphisms among BCG daughter strains, but lacked the resolution to identify s...

  12. Múltiplas doses de vacina BCG podem proteger contra asma? Can multiple doses of BCG vaccine protect against asthma?

    Directory of Open Access Journals (Sweden)

    Emanuel Sarinho

    2010-06-01

    Full Text Available OBJETIVO: Comparar a vacinação com uma única dose de BCG intradérmica com a vacinação com múltiplas doses, uma das quais pela técnica de multipuntura, em relação ao efeito protetor contra o aparecimento posterior de asma. MÉTODOS: Estudo de coorte retrospectivo com 2.311 pessoas vacinadas com BCG. Os indivíduos foram classificados de acordo com o número de doses de vacina BCG recebidas (uma dose, duas doses e três ou mais doses. O tempo mínimo de acompanhamento para verificar se houve algum efeito protetor da vacina BCG em relação ao diagnóstico de asma foi de 10 anos. RESULTADOS: A amostra incluiu 1.317 pessoas (56,99% que receberam apenas uma dose do BCG, 644 (27,87% que receberam duas doses e 350 (15,14% com três ou mais doses. O número de pacientes diagnosticados com asma entre aqueles que receberam uma dose de BCG, duas doses e três ou mais doses foi, respectivamente, 216 (16,40%, 107 (16,61% e 50 (14,28%. Não houve diferenças significativas entre os grupos. CONCLUSÕES: Na amostra estudada, não foi observada uma redução na prevalência de diagnóstico de asma com a revacinação ou com o uso de múltiplas doses da vacina BCG.OBJECTIVE: To compare BCG vaccination involving a single intradermal dose and that involving multiple doses, one given with the multiple puncture technique, in terms of the protective effect against the subsequent onset of asthma. METHODS: A retrospective cohort study involving 2,311 individuals having received the BCG vaccine. The patients were classified according to the number of doses of BCG vaccine administered (one; two; or three or more. The minimum follow-up period in order to determine whether there was any protective effect of BCG vaccination regarding the diagnosis of asthma was 10 years. RESULTS: The sample included 1,317 individuals (56.99% who had received only one BCG dose, 644 (27.87% who had received two doses, and 350 (15.14% who had received three or more doses. The number

  13. Comparison of the immunogenicity and protection against bovine tuberculosis following immunization by BCG-priming and boosting with adenovirus or protein based vaccines.

    Science.gov (United States)

    Dean, G; Whelan, A; Clifford, D; Salguero, F J; Xing, Z; Gilbert, S; McShane, H; Hewinson, R G; Vordermeier, M; Villarreal-Ramos, B

    2014-03-01

    There is a requirement for vaccines or vaccination strategies that confer better protection against TB than the current live attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine for use in cattle. Boosting with recombinant viral vectors expressing mycobacterial proteins, such as Ag85A, has shown a degree of promise as a strategy for improving on the protection afforded by BCG. Experiments in small animal models have indicated that broadening the immune response to include mycobacterial antigens other than Ag85A, such as Rv0288, induced by boosting with Ad5 constructs has a direct effect on the protection afforded against TB. Here, we compared the immunogenicity and protection against challenge with M. bovis afforded by boosting BCG-vaccinated cattle with a human type 5 (Ad5)-based vaccine expressing the mycobacterial antigens Ag85A (Ad5-85A); or Ag85A, Rv0251, Rv0287 and Rv0288 (Ad5-TBF); or with protein TBF emulsified in adjuvant (Adj-TBF). Boosting with TBF broaden the immune response. The kinetics of Ad5-TBF and Adj-TBF were shown to be different, with effector T cell responses from the latter developing more slowly but being more durable than those induced by Ad5-TBF. No increase in protection compared to BCG alone was afforded by Ad5-TBF or Adj-TBF by gross pathology or bacteriology. Using histopathology, as a novel parameter of protection, we show that boosting BCG vaccinated cattle with Ad5-85A induced significantly better protection than BCG alone. PMID:24269321

  14. Enhancement of Leishmania amazonensis infection in BCG non-responder mice by BCG-antigen specific vaccine

    Directory of Open Access Journals (Sweden)

    Kátia da Silva Calabrese

    1992-01-01

    Full Text Available Different patterns of cutaneous leishmaniasis can be induced when a challenge of alike dose of Leishmania amazonensis amastigotes in various inbred strains was applied. Two strains of mice, the Balb/c and C57 BL/10J, showed exceptional suscepbility, and 10(elevado a sexta potência amastigotes infective dose lead, to ulcerative progressive lesions with cutaneous metastasis and loss by necrosis of leg on wich the footpad primary lesion occured. Lesions were also progressive but in a lower degree when C3H/HeN and C57BL/6 were infected. Lesions progress slowly in DBA/2 mice presenting lesions wich reach a discreet peack after 12 weeks, do not heal but do not uncerate. DBA/2 mice is, therefore, a good model for immunomodualtion. In attempt to determine the influence of BCG in vaccination schedule using microsomal fraction, DBA/2 became an excellent model, since it is also a non-responder to BCG. Vaccination of DBA/2 mice, receiving the same 10(elevado a sexta potência BCG viable dose and 10 *g or 50 *g of protein content of microsomal fraction, lead to a progressive disease with time course similar to those observed in susceptible non-vaccinated C57BL/10J mice after 6 months of observation. An enhancement of infection in BCG non-responder mice suggests that use of BCG as immunostimulant in humans could be critical for both vaccination and immunoprophylactic strategies.

  15. Recombinant Mycobacterium bovis BCG as an HIV vaccine vector.

    Science.gov (United States)

    Chapman, Rosamund; Chege, Gerald; Shephard, Enid; Stutz, Helen; Williamson, Anna-Lise

    2010-06-01

    HIV-1 has resulted in a devastating AIDS pandemic. An effective HIV/AIDS vaccine that can be used to either, prevent HIV infection, control infection or prevent progression of the disease to AIDS is needed. In this review we discuss the use of Mycobacterium bovis BCG, the tuberculosis vaccine, as a vaccine vector for an HIV vaccine. Numerous features make BCG an attractive vehicle to deliver HIV antigens. It has a good safety profile, elicits long-lasting cellular immune responses and in addition manufacturing costs are affordable, a necessary consideration for developing countries. In this review we discuss the numerous factors that influence generation of a genetically stable recombinant BCG vaccine for HIV. PMID:20353397

  16. Whole-Genome Sequences of Four Mycobacterium bovis BCG Vaccine Strains ▿

    OpenAIRE

    Pan, Yuanlong; Yang, Xi; Duan, Jia; Lu, Na; Leung, Andrea S.; Tran, Vanessa; Hu, Yongfei; Wu, Na; Liu, Di; Wang, Zhiming; Yu, Xuping; Chen, Chen; Zhang, Yuanyuan; Wan, Kanglin; LIU Jun

    2011-01-01

    Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only vaccine available against tuberculosis (TB). A number of BCG strains are in use, and they exhibit biochemical and genetic differences. We report the genome sequences of four BCG strains representing different lineages, which will help to design more effective TB vaccines.

  17. Immunotherapy with BCG cell wall plus irradiated tumor cells

    International Nuclear Information System (INIS)

    Two different fibrosarcomas (MCB-I, MCB-II) were induced by methylcholcholanthrene in syngeneic Balb/C mice were used. The tumor cells irradiated with 5,000 to 30,000 rads did not growth in mice on 30 days after inoculation. The viable tumor cells were challenged intradermally to mice on 7 days after inoculation of the tumor cells irradiated with 5,000 to 30,000 rads. The challenged tumor cells were all rejected at 30 days after inoculation. Mice were challenged with 5 x 105 viable tumor cells on 7 days after inoculation of 103 to 108 irradiated tumor cells. Mice pretreated with 105 or 106 irradiated tumor cells rejected the tumor cells completely. The viable tumor cells were challenged to mice on 7 days after inoculation of BCG-CW emulsion plus 106 irradiated tumor cells. 0, 50, 100, 200, and 400 mu g of BCG-CW emulsion were mixed in 106 irradiated tumor cells. Optimal dosage of BCG-CW emulsion was 50 or 100 mu g. BCG-CW emulsion plus irradiated tumor cells were injected subcutaneously to the mice after tumor cells inoculation. Three injections of the vaccine significantly suppressed the tumor outgrowth, but not one or two injections in no-treated mice. However, in the mice pretreated with BCG-CW emulsion, the tumor growth was significantly suppressed by one or two injections of the vaccine. Especially, the three injections of the vaccine significantly suppressed the tumor growth and the 25% of the mice were completely cured. The effect of the vaccine was almost the same grade by contralateral or ipsilateral treatment. The irradiated MCB-II tumor cells plus BCG-CW emulsion were not effective to the MCB-1 tumor bearing mice, suggesting the anti-tumor effect of this vaccine was immunologically specific

  18. Immunotherapy with BCG cell wall plus irradiated tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Mizukuro, Tomoyuki (Kyoto Prefectural Univ. of Medicine (Japan))

    1983-04-01

    Two different fibrosarcomas (MCB-I, MCB-II) were induced by methylcholcholanthrene in syngeneic Balb/C mice were used. The tumor cells irradiated with 5,000 to 30,000 rads did not growth in mice on 30 days after inoculation. The viable tumor cells were challenged intradermally to mice on 7 days after inoculation of the tumor cells irradiated with 5,000 to 30,000 rads. The challenged tumor cells were all rejected at 30 days after inoculation. Mice were challenged with 5 x 10/sup 5/ viable tumor cells on 7 days after inoculation of 10/sup 3/ to 10/sup 8/ irradiated tumor cells. Mice pretreated with 10/sup 5/ or 10/sup 6/ irradiated tumor cells rejected the tumor cells completely. The viable tumor cells were challenged to mice on 7 days after inoculation of BCG-CW emulsion plus 10/sup 6/ irradiated tumor cells. 0, 50, 100, 200, and 400 mu g of BCG-CW emulsion were mixed in 10/sup 6/ irradiated tumor cells. Optimal dosage of BCG-CW emulsion was 50 or 100 mu g. BCG-CW emulsion plus irradiated tumor cells were injected subcutaneously to the mice after tumor cells inoculation. Three injections of the vaccine significantly suppressed the tumor outgrowth, but not one or two injections in no-treated mice. However, in the mice pretreated with BCG-CW emulsion, the tumor growth was significantly suppressed by one or two injections of the vaccine. Especially, the three injections of the vaccine significantly suppressed the tumor growth and the 25% of the mice were completely cured. The effect of the vaccine was almost the same grade by contralateral or ipsilateral treatment. The irradiated MCB-II tumor cells plus BCG-CW emulsion were not effective to the MCB-1 tumor bearing mice, suggesting the anti-tumor effect of this vaccine was immunologically specific.

  19. Recombinant Mycobacterium bovis BCG as an HIV Vaccine Vector

    OpenAIRE

    Chapman, Rosamund; Chege, Gerald; Shephard, Enid; Stutz, Helen; Williamson, Anna-Lise

    2010-01-01

    HIV-1 has resulted in a devastating AIDS pandemic. An effective HIV/AIDS vaccine that can be used to either, prevent HIV infection, control infection or prevent progression of the disease to AIDS is needed. In this review we discuss the use of Mycobacterium bovis BCG, the tuberculosis vaccine, as a vaccine vector for an HIV vaccine. Numerous features make BCG an attractive vehicle to deliver HIV antigens. It has a good safety profile, elicits long-lasting cellular immune responses and in addi...

  20. Up-date of the BCG code library

    International Nuclear Information System (INIS)

    Procedures for generating an up-date material library for the BCG code were established. A new library was generated by processing ENDF/B-IV data with the 89-1 version of the LINEAR, RECENT and SIGMA1 programs. The effect of library change in the neutron spectrum and effective multiplication factor of a fast reactor cell was analized. During the course of this study, an error was detected in the BCG code. Although localized in a narrow energy range, the discrepancies in neutron spectrum caused by the error were large enough to yield a difference of about 1% in the effective multiplication factor of the test cell. (author)

  1. Cutaneous necrotic ulceration due to BCG re-vaccination

    DEFF Research Database (Denmark)

    Gyldenløve, Mette; Andersen, Ase Bengård; Halkjær, Liselotte Brydensholt

    2012-01-01

    The case report describes a severe local reaction with large cutaneous necrotic ulcer following bacillus Calmette-Guérin (BCG) re-vaccination. This is a very rare adverse event, and only a few reports have been described in the literature.......The case report describes a severe local reaction with large cutaneous necrotic ulcer following bacillus Calmette-Guérin (BCG) re-vaccination. This is a very rare adverse event, and only a few reports have been described in the literature....

  2. Immunostimulatory Activity of Recombinant Mycobacterium bovis BCG That Secretes Major Membrane Protein II of Mycobacterium leprae

    OpenAIRE

    Makino, Masahiko; Maeda, Yumi; Inagaki, Katsuya

    2006-01-01

    We previously demonstrated that major membrane protein II (MMP-II) is one of the immunodominant antigens (Ags) of Mycobacterium leprae capable of activating T cells through Toll-like receptor 2. Based on the observation that Mycobacterium bovis BCG secreting a 30-kDa protein offered better protection against tuberculosis, we constructed a recombinant BCG strain (BCG-SM) that secretes MMP-II to improve the potency of BCG against leprosy. The secreted MMP-II protein from BCG-SM stimulated monoc...

  3. Assessment of immunological markers and booster effects of Ag85B peptides, Ag85B, and BCG in blood of BCG vaccinated children: a preliminary report

    OpenAIRE

    Husain, Aliabbas A.; Daginawala, Hatim F.; Singh, Lokendra; Kashyap, Rajpal S

    2016-01-01

    Purpose In the present study, the protective immunological markers in serum and peripheral blood mononuclear cells (PBMCs) of bacillus Calmette–Guérin (BCG) vaccinated and unvaccinated children were evaluated after vaccination. Further, PBMCs of children with low protective levels were boosted with BCG, Ag85B, and Ag85B peptides to study their booster effects to increase waning BCG induced immunity. Materials and Methods Fifty children from 1 month to 18 years of age were randomized for the s...

  4. Genomic and proteomic analyses of Mycobacterium bovis BCG Mexico 1931 reveal a diverse immunogenic repertoire against tuberculosis infection

    OpenAIRE

    López-Vidal Yolanda; Mendoza-Hernández Guillermo; Hernández-González Ismael L; Arvizu Adriana; Cevallos Miguel A; de León Samuel; Orduña Patricia

    2011-01-01

    Abstract Background Studies of Mycobacterium bovis BCG strains used in different countries and vaccination programs show clear variations in the genomes and immune protective properties of BCG strains. The aim of this study was to characterise the genomic and immune proteomic profile of the BCG 1931 strain used in Mexico. Results BCG Mexico 1931 has a circular chromosome of 4,350,386 bp with a G+C content and numbers of genes and pseudogenes similar to those of BCG Tokyo and BCG Pasteur. BCG ...

  5. New vaccines against tuberculosis: lessons learned from BCG immunisation in Brazil.

    Science.gov (United States)

    Antas, P R Z; Castello-Branco, L R R

    2008-07-01

    The current tuberculosis (TB) vaccine Mycobacterium bovis BCG has been employed for some 70 years in Brazil and lessons from its use should be taken in account for the development or improvement of new TB vaccines. The vast majority of the current population has been vaccinated with BCG, with the possible requirement for a booster immunisation in adulthood for TB protection. BCG Moreau strain also protects against leprosy, meningitis and extrapulmonary forms of TB. Factors related to differences in strain, dosage and BCG administering protocol have been responsible for the variable efficacy of BCG. This vaccine is clearly affected by, as yet unclear, host and/or environmental variables. In this brief review, we describe some aspects of BCG immunisation observed in Brazil that may be of importance for improving or replacing BCG. PMID:18440575

  6. Oral Polio Vaccine Influences the Immune Response to BCG Vaccination. A Natural Experiment

    DEFF Research Database (Denmark)

    Sartono, E.; Lisse, I.M.; Terveer, E.M.; van de Sande, P.J.M.; Whittle, H.; Fisker, Bent; Roth, A.; Aaby, Peter; Yazdanbakhsh, M.; Benn, Christine Stabell

    2010-01-01

    Background: Oral polio vaccine (OPV) is recommended to be given at birth together with BCG vaccine. While we were conducting two trials including low-birth-weight (LBW) and normal-birth-weight (NBW) infants in Guinea-Bissau, OPV was not available during some periods and therefore some infants did...... not receive OPV at birth, but only BCG. We investigated the effect of OPV given simultaneously with BCG at birth on the immune response to BCG vaccine. Methods and Findings: We compared the in vitro and the in vivo response to PPD in the infants who received OPV and BCG with that of infants who...... with OPV. Worryingly, the results indicate that the common practice in low-income countries of administering OPV together with BCG at birth may down-regulate the response to BCG vaccine...

  7. Protection Induced by Simultaneous Subcutaneous and Endobronchial Vaccination with BCG/BCG and BCG/Adenovirus Expressing Antigen 85A against Mycobacterium bovis in Cattle

    OpenAIRE

    Dean, GS; Clifford, D.; Whelan, AO; Tchilian, EZ; Beverley, PCL; Salguero, FJ; Z. Xing; Vordermeier, HM; Villarreal-Ramos, B

    2015-01-01

    The incidence of bovine tuberculosis (bTB) in the GB has been increasing since the 1980s. Immunisation, alongside current control measures, has been proposed as a sustainable measure to control bTB. Immunisation with Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been shown to protect against bTB. Furthermore, much experimental data indicates that pulmonary local immunity is important for protection against respiratory infections including Mycobacterium tuberculosis and that pulmonary...

  8. ANALISIS MATRIKS BOSTON CONSULTING GROUP (BCG) UNTUK MEMENANGKAN STRATEGI ORGANISASI

    OpenAIRE

    Haryadi Sarjono; Engkos Achmad Kuncoro

    2013-01-01

    Penelitian ini bertujuan untuk mengetahui posisi tingkat pertumbuhan pasar pada perguruan tinggi khususnya Sekolah Tinggi berdasarkan market share, menggunakan matriks BCG. Unit analisis adalah semua perguruan tinggi swasta yang termasuk dalam Kopertis Wilayah III DKI Jakarta, yang terdiri dari Universitas, Sekolah Tinggi, Institut, dan Akademi. Objek analisis adalah jumlah penerimaan mahasiswa baru. Metode pengumpulan data yang dilakukan dalam penulisan ini adalah dengan metode ...

  9. Mechanisms of cell accumulation induced by Mycobacterium bovis BCG

    Directory of Open Access Journals (Sweden)

    Octávio Menezes-de-Lima-Júnior

    1997-12-01

    Full Text Available Mycobacteria, specially Mycobacterium tuberculosis are among the micro-organisms that are increasing dramatically the number of infections with death, all over the world. A great number of animal experimental models have been proposed to investigate the mechanisms involved in the host response against these intracellular parasites. Studies of airway infection in guinea-pigs and rabbits, as well as, in mice intravenously infected with BCG have made an important contribution to our understanding of the virulence, pathogenesis and the immunology of mycobacterial infections. Although, there are few models to study the mechanisms of the initial inflammatory process induced by the first contact with the Mycobacteria, and the relevance of the acute generation of inflammatory mediators, cytokines and leukocyte infiltration to the development of the mycobacterial infection. In this work we reviewed our results obtained with a model of M. bovis BCG-induced pleurisy in mice, describing the mechanisms involved in the leukocyte influx induced by BCG at 24 hr. Different mechanisms appear to be related with the influx of neutrophils, eosinophils and mononuclear cells and distinct inflammatory mediators, cytokines and adhesion molecules are involved in the BCG-induced cell accumulation.

  10. Trained immunity: consequences for the heterologous effects of BCG vaccination

    NARCIS (Netherlands)

    Kleinnijenhuis, J.; Crevel, R. van; Netea, M.G.

    2015-01-01

    A growing body of evidence from epidemiologic and immunologic studies have shown that in addition to target disease-specific effects, vaccines have heterologous effects towards unrelated pathogens. Like some other vaccines, bacille Calmette-Guerin (BCG) has shown in observational studies and randomi

  11. Post BCG Lymphadenitis in Vaccinated Infants in Yazd, Iran

    Directory of Open Access Journals (Sweden)

    Mostafa Behjati

    2008-12-01

    Full Text Available Objective: Bacille Calmette-Guَerin (BCG vacination is performed as a part of expanded program of immunization (EPI. Lymphadenitis is the most common complication of BCG vaccination. The aim of this study was to determine the incidence and natural course of BCG lymphadenitis vaccinated in Yazd, Iran.Methods: In this analytical prospective follow up study a total of 480 (240 females and 240 males consecutive newborns received 0.05 ml of BCG vaccine intradermally on right arm within the first week of life during April to July 2003. These babies were followed up when 1.5, 3, 4.5, 6 and 9 months old. Findings: A total of 26 (5.8% cases of lymphadenitis were detected. Lymphadenitis occurred as ipsilateral axillary nodes in 24 (92.3% cases, supraclavicular in one (3.8% case, and supraclavicular in association with axillary nodes in one case (3.8%. Infants developed lymphadenitis during 4 wks of life in one (3.84% case, between first and fourth month of life in 14 (53.8% cases, and between fourth and sixth month of life in 11 (42.3% cases. All 26 cases of lymphadenitis were followed up for 9 months. Twenty two (84.6% cases were simple or non-suppurative and 4 (15.4% cases suppurative lymphadenitis. Eleven (42.3% cases of non-suppurative lymphadennitis showed spontanous resolution and eleven (42.3% cases had partial regression without progression or drainage. Four (15.4% cases developed suppuration with one (3.8% case of fistulation and drainage. Conclusion: The greater incidence of lymphadenopathy in our cases can probably be attributed to a more immunogenic vaccine (Pasteur institute, Tehran, young vaccinees (newborn infants, injection in the right arm or improper dilution. Non-suppurative BCG lymphadenitis is a benign condition and regresses spontanously without any treatment.

  12. Local skin reaction following an accidental injection from a BCG vaccine in a healthcare worker

    Directory of Open Access Journals (Sweden)

    Kundan Mittal

    2011-02-01

    Full Text Available Exposure to blood-borne pathogens from sharp injuriescontinue to pose a significant risk to healthcare workers(HCW. The number of sharps injuries sustained by HCW is stillunclear, primarily due to under-reporting of events.Healthcare professionals are at risk of sustaining such injuriesfrom hollow-bore needles. Sharps injuries are associated withrisk of infection with blood-borne pathogens such as humanimmunodeficiency virus (HIV, hepatitis B virus (HBV hepatitisC virus (HCV and other live organisms. Here we are reportinga case of an adverse reaction in a HCW due to an accidentalsharps injury by a needle used to administer the BacillusCalmittee Gurien (BCG vaccine.

  13. BCG immunotherapy of bladder cancer: inhibition of tumor recurrence and associated immune responses.

    Science.gov (United States)

    Lamm, D L; Thor, D E; Winters, W D; Stogdill, V D; Radwin, H M

    1981-07-01

    Fifty-one patients with confirmed bladder cancer have enrolled in a prospective evaluation of BCG immunotherapy. Following resection of existing tumors, patients were stratified according to tumor grade and number of previous recurrences and randomly assigned to control or BCG treatment groups. Immunotherapy consisted of six weekly administrations of Pasteur strain BCG using 120 mg intravesically and 5 mg percutaneously. Immunotherapy side effects were minimal and no patient required postponement of BCG treatments. Eleven control (46%) compared with five (22%) BCG-treated patients had tumor recurrence (P = 0.078, chi 2). Prolongation of the disease-free interval with BCG treatment was significantly at the P = 0.016 level by Wilcoxon analysis. Four control and two BCG-treated patients had multiple recurrences. Comparing total episodes of recurrence, nineteen of 79 (24%) control and eight of 85 (7%) BCG group cystoscopic examinations revealed tumor (P = 0.006, chi 2). Immunologic correlates of response to immunotherapy were not statistically significant since only five BCG-treated patients had tumor recurrence. However, four of these five patients evidenced impaired LIF response to PPD at the time of tumor recurrence, and impairment of skin test reactivity and BCG humoral antibody response were more commonly seen in this subgroup of patients. PMID:7016300

  14. Effectiveness of BCG Vaccination in Prevention of Childhood Tuberculosis: A Prospective Study from Kishanganj, Bihar

    Directory of Open Access Journals (Sweden)

    Kashif Shahnawaz, Goutam Sarkar, Palash Das, Mausumi Basu, Biman Roy

    2013-01-01

    Full Text Available Introduction: BCG vaccine has shown consistently high efficacy against childhood tubercular meningitis and miliary tuberculosis and other mycobacterial diseases. It is considered to be a safe vaccine with a low incidence of adverse effects. Efficacy of BCG vaccine found in different clinical trials is variable in different geography. Objectives: Study was done to assess the efficacy of BCG vac-cine. Materials and Methods: All the children who were less than three years of age and were previously BCG vaccinated and not-vaccinated, were included in this study. A total of sixty (60 vaccinated children and sixty non-vaccinated children were selected. These children were followed up prospectively for 24 months, at the end of which, it was seen whether they developed tuberculosis or not. Results: Out of these 60 children in both the cases and control groups, total number of BCG vaccinated children who developed TB were 4 (i.e. 6.6% and total number of Non-BCG vaccinated children who developed TB were 12 (i.e. 20%. Thus, the efficacy of BCG vaccine calculated in our study was 67%. Conclusion: Most studies in different parts of the world have shown that the efficacy of BCG vaccine varies from zero to eigh-ty percent. This study favors the efficacy of BCG vaccine. This vaccination strategy will be favorable for our children. Creation of awareness among the parents and family members for an early administration of BCG vaccine after child birth can be recom-mended.

  15. Added value of use of a purified protein derivative-based enzyme-linked immunosorbent spot assay for patients with Mycobacterium bovis BCG infection after intravesical BCG instillations.

    Science.gov (United States)

    Heemstra, Karen A; Bossink, Ailko W J; Spermon, Roan; Bouwman, John J M; van der Kieft, Robert; Thijsen, Steven F T

    2012-06-01

    In this case series, we describe four cases in which the use of gamma interferon release assays with purified protein derivative (PPD) as a stimulating antigen was able to demonstrate PPD-specific immune activation. This may help to improve the adequate diagnosis of (systemic) Mycobacterium bovis BCG infections after intravesical BCG instillations for bladder carcinoma. PMID:22461529

  16. Added Value of Use of a Purified Protein Derivative-Based Enzyme-Linked Immunosorbent Spot Assay for Patients with Mycobacterium bovis BCG Infection after Intravesical BCG Instillations

    OpenAIRE

    Heemstra, Karen A.; Bossink, Ailko W. J.; Spermon, Roan; Bouwman, John J. M.; van der Kieft, Robert; Thijsen, Steven F. T.

    2012-01-01

    In this case series, we describe four cases in which the use of gamma interferon release assays with purified protein derivative (PPD) as a stimulating antigen was able to demonstrate PPD-specific immune activation. This may help to improve the adequate diagnosis of (systemic) Mycobacterium bovis BCG infections after intravesical BCG instillations for bladder carcinoma.

  17. IMPROVEMENT OF THE RICHNESS ESTIMATES OF maxBCG CLUSTERS

    International Nuclear Information System (INIS)

    Minimizing the scatter between cluster mass and accessible observables is an important goal for cluster cosmology. In this work, we introduce a new matched filter richness estimator, and test its performance using the maxBCG cluster catalog. Our new estimator significantly reduces the variance in the LX -richness relation, from σlnLx2 = (0.86±0.02)2 to σlnLx2 = (0.69±0.02)2. Relative to the maxBCG richness estimate, it also removes the strong redshift dependence of the LX -richness scaling relations, and is significantly more robust to photometric and redshift errors. These improvements are largely due to the better treatment of galaxy color data. We also demonstrate the scatter in the LX -richness relation depends on the aperture used to estimate cluster richness, and introduce a novel approach for optimizing said aperture which can easily be generalized to other mass tracers.

  18. Orientations pour l'intégration des TICE dans l'enseignement du français en Syrie. L'exemple du centre de documentation pédagogique de Damas.

    Directory of Open Access Journals (Sweden)

    Christelle Demange-Ducrot

    2005-09-01

    Full Text Available Le secteur éducatif syrien souhaite orienter son action vers les nouvelles technologies de l'information et la sensibilisation du public scolaire aux applications de l'informatique dans le domaine éducatif et en particulier dans le cadre de l'enseignement des langues. Dans l'enseignement-apprentissage des langues, les apports des TICE sont nombreux, mais là où elles apportent sans doute la plus grande plus-value, c'est lors de la mise en place de projets de classe motivants et valorisants, intégrés à des projets de communication authentique. Partant de ce constat, le Centre de Documentation Pédagogique de Damas forme les enseignants de français syriens à l'intégration des TICE dans des projets pédagogiques de classe mettant en œuvre des activités créatives et stimulantes pour communiquer en français. Jusqu'alors, les formations ont centré leurs efforts sur les bases de l'environnement informatique et de la bureautique, avec pour parti pris l'utilisation de logiciels libres. L'année 2005 marquera le lancement et l'expérimentation du dispositif de formation continue à distance destiné aux professeurs de français dans le domaine des TICE.

  19. [Comparative study of two dried intradermal BCG vaccines (author's transl)].

    Science.gov (United States)

    Fillastre, C; Guerin, N; Danusantoso, H; Sardadi, S

    1979-01-01

    Two BCG vaccines prepared from the same strain were studied clinically in Indonesia and in France. The concentration in culturable particles was comparable. Observed differences in the Mantoux results are discussed. The French results, based on use in a temperate climate by a specialized team, on well nourished children, appear better than the Indonesian findings. Further steps should be undertaken to improve results in Indonesia. PMID:539694

  20. The Young face of the BCG ESO 400-G43

    International Nuclear Information System (INIS)

    We briefly discuss the results of a multifrequency study of the blue compact galaxy ESO 400-G43. This galaxy, one of the most luminous BCG:s known, is embedded in a massive HI cloud and shows clear signs of a global burst of star formation. There are substantial evidence that this is the first grand star formation epoch in the history of this galaxy

  1. Serial subcultivation of Czechoslovakian and Japanese BCG strains.

    Science.gov (United States)

    Osborn, T W

    1980-10-01

    Changes in the Danish BCG strain under certain regimens of subculture have been shown in preceding studies to be associated with selection of a minority population. Three Czechoslovakian BCG strains, all originally derived from the Danish strain but thereafter and in distinction from it maintained on potato media, have now been investigated. Changes in the immunizing potency of two of these strains have been attributed by other workers to employment of the richer potato media in place of Sauton medium as used for maintenance of the parent Danish strain. However, results from the present study suggest rather that selection of a pre-existing minority genotype or of a new mutant occurred. This proposal is supported by the finding that the third strain has maintained characteristics similar to those of the Danish parent despite many previous transfers on potato media.Another BCG strain investigated was the Japanese which, like the three Czechoslovakian strains, had been previously maintained on potato media. This strain has been shown in the present study to resemble the Danish strain in supporting a minority population yielding non-spreading colonies. Czechoslovakian vaccine prepared with seed culture supplied from Tokyo has retained characteristics similar to those of the Japanese parent. Although a majority population yielding spreading colonies appears so far to have been retained in both centres, it is considered that selection of the minority could still occur in the course of routine transfer. PMID:7005326

  2. A NOVEL BCG SENSOR-ARRAY FOR UNOBTRUSIVE CARDIAC MONITORING

    Directory of Open Access Journals (Sweden)

    Anna Böhm

    2013-12-01

    Full Text Available Unobtrusive heart rate monitoring is a popular research topic in biomedical engineering. The reason is that convential methods, e.g. the clinical gold standard electrocardiography, require conductive contact to the human body. Other methods such as ballistocardiography try to record these vital signs without electrodes that are attached to the body. So far, these systems cannot replace routine procedures. Most systems have some drawbacks that cannot be compensated, such as aging of the sensor materials or movement artifacts. In addition, the signal form differs greatly from an ECG, which is an electrical signal. The ballistocardiogram has a mechanical source, which makes it harder to evaluate. We have developed a new sensor array made of near-IR-LEDs to record BCGs. IR-sensors do not age in relevant time scales. Analog filtering was neccesary, because the signal amplitude was very small. The digitized data was then processed by various algorithms to extract beat-to-beat or breath-to-breath intervals. The redundancy of multiple BCG channels was used to provide a robust estimation of beat-to-beat intervals and heart rate. We installed the system beneath a mattress topper of a hospital bed, but any other bed would have been sufficient. The validation of this measurement system shows that it is well suited for BCG recordings. The use of multiple channels has proven to be superior to relying on a single BCG channel.

  3. Active Mycobacterium Infection Due to Intramuscular BCG Administration Following Multi-Steps Medication Errors

    OpenAIRE

    MohammadReza Rafati; Bizhan Kouchaki

    2015-01-01

    Bacillus Calmette-Guérin (BCG) is indicated for treatment of primary or relapsing flat urothelial cell carcinoma in situ (CIS) of the urinary bladder. Disseminated infectious complications occasionally occur due to BCG as a vaccine and intravesical therapy.  Intramuscular (IM) or Intravenous (IV) administrations of BCG are rare medication errors which are more probable to produce systemic infections. This report presents 13 years old case that several steps medication errors occurred conseque...

  4. BCG Artifact Removal for Reconstructing Full-scalp EEG inside the MR Scanner

    OpenAIRE

    Xia, Hongjing; Ruan, Dan; Cohen, Mark S.

    2013-01-01

    In simultaneous EEG/fMRI acquisition, the ballistocardiogram (BCG) artifact presents a major challenge for meaningful EEG signal interpretation and needs to be removed. This is very difficult, especially in continuous studies where BCG cannot be removed with averaging. In this study, we take advantage of a high-density EEG-cap and propose an integrated learning and inference approach to estimate the BCG contribution to the overall noisy recording. In particular, we present a special-designed ...

  5. Preclinical Development of an In Vivo BCG Challenge Model for Testing Candidate TB Vaccine Efficacy

    OpenAIRE

    2011-01-01

    There is an urgent need for an immunological correlate of protection against tuberculosis (TB) with which to evaluate candidate TB vaccines in clinical trials. Development of a human challenge model of Mycobacterium tuberculosis (M.tb) could facilitate the detection of such correlate(s). Here we propose a novel in vivo Bacille Calmette-Guérin (BCG) challenge model using BCG immunization as a surrogate for M.tb infection. Culture and quantitative PCR methods have been developed to quantify BCG...

  6. Effectiveness of BCG Vaccination in Prevention of Childhood Tuberculosis: A Prospective Study from Kishanganj, Bihar

    OpenAIRE

    Kashif Shahnawaz, Goutam Sarkar, Palash Das, Mausumi Basu, Biman Roy

    2013-01-01

    Introduction: BCG vaccine has shown consistently high efficacy against childhood tubercular meningitis and miliary tuberculosis and other mycobacterial diseases. It is considered to be a safe vaccine with a low incidence of adverse effects. Efficacy of BCG vaccine found in different clinical trials is variable in different geography. Objectives: Study was done to assess the efficacy of BCG vac-cine. Materials and Methods: All the children who were less than three years of age and were...

  7. Oncogenic activation of Pak1-dependent pathway of macropinocytosis determines BCG entry into bladder cancer cells

    OpenAIRE

    Redelman-Sidi, Gil; Iyer, Gopa; Solit, David; Glickman, Michael S.

    2013-01-01

    Bacille Calmette-Guerin (BCG) is an attenuated strain of Mycobacterium bovis that is used widely as a vaccine for tuberculosis and is used as an effective treatment for superficial bladder carcinoma. Despite being the most successful cancer biotherapy, its mechanism of action and response determinants remain obscure. Here we establish a model system to analyze BCG interaction with bladder cancer cells, using it to show that these cells vary dramatically in their susceptibility to BCG infectio...

  8. In vitro culture medium influences the vaccine efficacy of Mycobacterium bovis BCG

    OpenAIRE

    Venkataswamy, Manjunatha M.; Goldberg, Michael F.; Baena, Andres; Chan, John; Jacobs, William R.; Porcelli, Steven A.

    2011-01-01

    The varied rates of protection induced by Mycobacterium bovis BCG vaccine against tuberculosis has been attributed to many factors such as genetic variability among BCG strains, rapid clearance of BCG in some populations, and different levels of previous exposure of vaccinated populations to environmental mycobacteria. However, the methods and conditions employed to prepare this vaccine for human usage by various manufacturers have not been investigated as potential factors contributing to th...

  9. Modification of death rate of irradiated mice by B.C.G

    International Nuclear Information System (INIS)

    Freeze-dried Bacillus Calmette Guerin (BCG) of Institut Pasteur was given by intravenous route to mice at 1,2 and 4mg/kg before and after γ irradiation of animals by 1000 rad. B.C.G. 1 mg/kg injected the day or the day after irradiation has a protective effect (mortality reduced from 77% for controls to 58% and 50% for treated mice). B.C.G. given before irradiation in single or double doses increased mortality

  10. The management of BCG failure in non-muscle-invasive bladder cancer: an update

    OpenAIRE

    Zlotta, Alexandre R.; Fleshner, Neil E.; Jewett, Michael A.

    2009-01-01

    Up to 40% of patients with non-muscle-invasive bladder cancer (NMIBC) will fail intravesical bacillus Calmette-Guérin (BCG) therapy. There is unfortunately no current gold standard for salvage intravesical therapy after appropriate BCG treatment. Indeed, outcomes are at best suboptimal. The vast majority of low-grade NMIBC are prone to recur but very rarely progress. Failure after intravesical BCG in these patients is usually superficial and low-grade. At the other end of the spectrum, failur...

  11. Prosthetic Joint Infection due to Mycobacterium bovis after Intravesical Instillation of Bacillus Calmette-Guerin (BCG

    Directory of Open Access Journals (Sweden)

    Eric Gomez

    2009-01-01

    Full Text Available Intravesical instillation of Bacillus Calmette-Guerin (BCG is a treatment to prevent recurrence of superficial urothelial bladder carcinoma. Complications after bladder instillation of BCG have been reported including locally invasive and systemic infections due to dissemination of Mycobacterium bovis from the bladder. We present an uncommon case and literature review of prosthetic joint infection due to M. bovis after intravesical BCG treatment of bladder cancer.

  12. Difference in antigen-presenting ability of macrophages between high- and low-responder mice in delayed-type hypersensitivity to Mycobacterium bovis BCG.

    OpenAIRE

    Nakamura, R. M.; Tokunaga, T; Yamamoto, S.

    1980-01-01

    Purified protein derivative-pulsed spleen macrophages of Mycobacterium bovis BCG high-responder mice stimulated BCG-primed lymphocytes of F1 (low x high) mice well in vitro, but those of BCG low-responder mice did not.

  13. Protective efficacy of BCG vaccine against leprosy in southern Malaŵi.

    OpenAIRE

    Baker, D. M.; Nguyen-Van-Tam, J. S.; Smith, S J

    1993-01-01

    This paper describes a matched case-control study to determine the efficacy of BCG vaccine in preventing the occurrence of leprosy in southern Malaŵi, a previously unstudied area. The BCG immunization rate amongst 145 individuals with leprosy was 44.8%, compared to 62.5% in 290 matched controls. The protective efficacy of BCG vaccine against leprosy in this region was estimated to be 63.6%; smallpox immunization had no effect. These findings support the view that BCG vaccine should be conside...

  14. Oral Polio Vaccine Influences the Immune Response to BCG Vaccination. A Natural Experiment

    OpenAIRE

    Sartono, Erliyani; Lisse, Ida M.; Terveer, Elisabeth M.; van de Sande, Paula J. M.; Whittle, Hilton; Fisker, Ane B; ROTH, ADAM; Aaby, Peter; Yazdanbakhsh, Maria; Benn, Christine S

    2010-01-01

    Background: Oral polio vaccine (OPV) is recommended to be given at birth together with BCG vaccine. While we were conducting two trials including low-birth-weight (LBW) and normal-birth-weight (NBW) infants in Guinea-Bissau, OPV was not available during some periods and therefore some infants did not receive OPV at birth, but only BCG. We investigated the effect of OPV given simultaneously with BCG at birth on the immune response to BCG vaccine. Methods and Findings: We compared the in vitro ...

  15. Active suppression of in vitro reactivity of spleen cells after BCG treatment

    International Nuclear Information System (INIS)

    It was found that spleen cells from mice injected i.v. with large doses of BCG responded to PHA stimulation less intensely than did normal spleen cells. It was shown that nylon wool column purified BCG treated T cells also had a low PHA reactivity. Unfractionated spleen cells, adherent cells or T-enriched populations from BCG treated mice, when added to normal T cells lowered their PHA reactivity. When the same BCG treated cell populations were added to tumor cells in vitro, they inhibited their growth. (author)

  16. Production of BCG alginate-PLL microcapsules by emulsification/internal gelation.

    Science.gov (United States)

    Esquisabel, A; Hernández, R M; Igartua, M; Gascón, A R; Calvo, B; Pedraz, J L

    1997-01-01

    A biocompatible emulsification method for microencapsulation of live cells and enzymes within a calcium alginate matrix applied to Bacillus Calmette-Guérin (BCG) has been developed. Small-diameter alginate beads (microcapsules) were formed via internal gelation of an alginate solution emulsified within vegetable oil. Five different oils (sesame, sweet almond, perhydrosqualene, camomile and jojoba) were used. The rheological analysis of the oils showed a Newtonian behaviour, with viscosities = 30.0, 37.7, 51.2, 59.3 and 67.1 mPa.s for perhydrosqualene, jojoba, camomile, sesame and sweet almond oil respectively. The particle size of the microcapsules obtained ranged from 30.3 microns for the microcapsules prepared with sweet almond oil to 57.0 microns for those made with perhydrosqualene. The mean particle diameter obtained was found to be dependent on the viscosity of the oil employed, according to the equation: phi (micron) = 76.6-0.628 eta (mPa.s) (r2 = 0.943). The encapsulated BCG was identified by the Difco TB stain set K, followed by observation under optical microscopy. Freeze-drying of the microcapsules was carried out to ensure their stability during storage. Two batches of microcapsules (those prepared with sesame and jojoba oil) and four types of cryoprotectors (glucose, trehalose, mannitol and sorbitol), at three concentration levels (5, 10 and 20% w/v) were studied. The parameters evaluated were particle size, physical appearance, reconstitution of lyophilizates and microscopical evaluation. For both batches of microcapsules the best results were obtained with trehalose 5%, showing particle sizes of 42.1 microns in the case of the microcapsules prepared with sesame oil, and of 45.3 microns for those prepared with jojoba. PMID:9292438

  17. Vacina BCG contra tuberculose: efeito protetor e políticas de vacinação BCG vaccine against tuberculosis: its protective effect and vaccination policies

    Directory of Open Access Journals (Sweden)

    Susan M Pereira

    2007-09-01

    Full Text Available OBJETIVO: A vacina BCG é utilizada desde 1921, embora ainda apresente controvérsias e aspectos não esclarecidos. O objetivo do artigo foi analisar aspectos relacionados ao efeito protetor da primeira e segunda doses da vacina BCG e as políticas de vacinação adotadas. MÉTODOS: Foi realizada revisão sistemática da literatura publicada em inglês e espanhol, abrangendo o período compreendido entre 1948 e 2006, na base PubMed. Os principais descritores utilizados foram BCG vaccine, BCG efficacy, BCG e tuberculosis. Os estudos foram agrupados por tipo de desenho, apresentando-se separadamente os principais resultados de ensaios clínicos, estudos de caso-controle e metanálises. RESULTADOS: O efeito protetor da primeira dose da vacina BCG contra a tuberculose na forma miliar ou na meningite é elevado. No entanto, os resultados são discordantes em relação à forma pulmonar, variando de ausência de efeito a níveis próximos a 80%. Estão sendo conduzidas pesquisas sobre novas vacinas candidatas a substituir a BCG ou serem utilizadas como reforço. CONCLUSÕES: Há evidências de que a segunda dose da BCG não aumenta o seu efeito protetor. Apesar de seus limites e da expectativa futura de nova vacina para tuberculose, a vacina BCG mantém-se como importante instrumento no controle dos efeitos danosos da doença, sobretudo em países com taxas de incidência médias e elevadas.OBJECTIVE: The BCG vaccine has been in use since 1921, but still arouses controversy and uncertainties. The objective was to analyze the protective effect of the BCG vaccine in its first and second doses and the accompanying vaccination policies. METHODS: A systematic review of the literature in both English and Spanish was carried out, covering the period 1948 to 2006, using the PubMed database. The main search terms used included BCG vaccine, BCG efficacy, BCG and tuberculosis. The studies were grouped by design, with the main results from the clinic tests, case

  18. Evaluation of a Human BCG Challenge Model to Assess Antimycobacterial Immunity Induced by BCG and a Candidate Tuberculosis Vaccine, MVA85A, Alone and in Combination

    OpenAIRE

    Harris, Stephanie A.; Meyer, Joel; Satti, Iman; Marsay, Leanne; Poulton, Ian D; Tanner, Rachel; Minassian, Angela M; Helen A. Fletcher; McShane, Helen

    2013-01-01

    Background. A new vaccine is urgently needed to combat tuberculosis. However, without a correlate of protection, selection of the vaccines to take forward into large-scale efficacy trials is difficult. Use of bacille Calmette-Guérin (BCG) as a surrogate for human Mycobacterium tuberculosis challenge is a novel model that could aid selection. Methods. Healthy adults were assigned to groups A and B (BCG-naive) or groups C and D (BCG-vaccinated). Groups B and D received candidate tuberculosi...

  19. Vaccination of cattle with Mycobacterium bovis BCG by a combination of systemic and oral routes.

    Science.gov (United States)

    Buddle, Bryce M; Denis, Michel; Aldwell, Frank E; Martin Vordermeier, H; Glyn Hewinson, R; Neil Wedlock, D

    2008-11-01

    Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine delivered to calves by the subcutaneous (s.c.) or by the oral route in a formulated lipid matrix has been previously shown to induce similar levels of protection against bovine tuberculosis. The current study was aimed at determining whether a combination of delivering BCG by s.c. and oral routes would enhance levels of protection, compared to only one route of vaccination. Forty calves were randomly divided into four groups (10/group). Calves were vaccinated with 10(6)colony forming units (CFU) of BCG Pasteur by the s.c. route or orally with 10(9)CFU BCG incorporated into a lipid formulation. One group received a combination of BCG administered by both the s.c. and oral routes and a non-vaccinated group served as a control. The two groups of calves that received s.c. BCG produced strong IFN-gamma responses in whole blood cultures stimulated with bovine purified protein derivative (PPD) 3 weeks after vaccination. Cattle vaccinated just with oral BCG in a lipid matrix produced a strong IFN-gamma response 8 weeks after vaccination, and peaking at 11 weeks after vaccination. All calves were challenged by the intratracheal route with M. bovis 15 weeks after vaccination and were euthanized and necropsied to assess protection at 17 weeks following challenge. BCG given s.c. or orally induced significant and comparable levels of protection against the virulent challenge. Vaccination of cattle by a combination of s.c./oral routes did not enhance protection beyond that achieved by s.c. or oral vaccination alone. We conclude that vaccination of cattle with BCG by a combination of routes has no beneficial additive effects, compared to a single s.c. administration of BCG or BCG given orally in a lipid formulation. PMID:18439875

  20. A Comprehensive Survey of Single Nucleotide Polymorphisms (SNPs) across Mycobacterium bovis Strains and M. bovis BCG Vaccine Strains Refines the Genealogy and Defines a Minimal Set of SNPs That Separate Virulent M. bovis Strains and M. bovis BCG Strains▿ †

    OpenAIRE

    Garcia Pelayo, M. Carmen; Uplekar, Swapna; Keniry, Andrew; Mendoza Lopez, Pablo; Garnier, Thierry; Nunez Garcia, Javier; Boschiroli, Laura; Zhou, Xiangmei; Parkhill, Julian; Smith, Noel; Hewinson, R Glyn; Cole, Stewart T.; Gordon, Stephen V.

    2009-01-01

    To further unravel the mechanisms responsible for attenuation of the tuberculosis vaccine Mycobacterium bovis BCG, comparative genomics was used to identify single nucleotide polymorphisms (SNPs) that differed between sequenced strains of Mycobacterium bovis and M. bovis BCG. SNPs were assayed in M. bovis isolates from France and the United Kingdom and from different BCG vaccines in order to identify those that arose during the attenuation process which gave rise to BCG. Informative data sets...

  1. Intégrer les Tice à une approche cognitive de la grammaire du discours How to integrate ICT into a cognitive approach of a discourse grammar?

    Directory of Open Access Journals (Sweden)

    Muriel Barbazan

    2011-09-01

    Full Text Available Si l'on a pour objectif de favoriser un apprentissage de la grammaire évaluable à l'aune des performances communicatives réelles des apprenants, il est utile d'identifier préalablement un cadre de travail qui respecte les processus cognitifs de production et de compréhension. Dans ce cadre, cet article envisage la question de la reformulation des contenus grammaticaux pour cibler l'apprentissage guidé de la langue telle qu'elle est mise en œuvre dans le "discours". Pour ce faire, on illustrera l'intérêt d'une démarche descriptive associant les deux pistes suivantes : a intégrer à la description grammaticale des prototypes de situations d'interactions verbales en relation avec les significations données aux outils grammaticaux. Parallèlement, b mettre en relation les fonctions des outils grammaticaux avec des types de plans textuels tout en insistant sur leur rôle de marqueurs de la macrostructure (repérage des unités textuelles. L'objet de cet article sera ensuite d'explorer les possibilités qu'offrent les Tice pour un apprentissage guidé ciblant l'acquisition de routines grammaticales adaptées à la production / réception du discours en situation. L'accent sera mis sur les activités de compréhension et de réorganisation unifiée des connaissances et savoir-faire grammaticaux, tout en soulignant l'intérêt des Tice pour favoriser en FLE la mise en œuvre effective et interactive de la L2. À partir d'exemples d'activités ou de possibilités d'exploitation de divers outils, cette seconde partie servira ainsi d'illustration aux axes descriptifs et aux orientations didactiques préalablement définis.In the light of results from psycholinguistics and cognitive psychology concerning learning models and verbal production processes, this article follows up two objectives. Before exploring the potential development of grammatical activities in a digital learning environment, the first part will explore how we can conceive

  2. Immunogenicity of Mycobacterium tuberculosis Antigens in Mycobacterium bovis BCG-Vaccinated and M. bovis-Infected Cattle

    OpenAIRE

    Mustafa, A. S.; Skeiky, Y A; Al-Attiyah, R.; Alderson, M. R.; Hewinson, R. G.; Vordermeier, H M

    2006-01-01

    The development of novel vaccine strategies supplementing Mycobacterium bovis BCG (BCG) constitutes an urgent research challenge. To identify potential subunit vaccine candidates, we have tested a series of eight recently identified Mycobacterium tuberculosis antigens in M. bovis-infected and BCG-vaccinated cattle. These antigens were characterized on the basis of their ability to induce in vitro gamma interferon responses in infected or BCG-vaccinated calves. We were able to establish a hier...

  3. Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

    OpenAIRE

    Hwang, Shen-An; Kruzel, Marian L.; Actor, Jeffrey K.

    2008-01-01

    The current vaccine for tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is an attenuated strain of Mycobacterium bovis bacillus Calmette-Guerin (BCG). BCG has proven to be effective in children, however, efficacy wanes in adulthood. Lactoferrin, a natural protein with immunomodulatory properties, is a potential adjuvant candidate to enhance efficacy of BCG. These studies define bovine lactoferrin as an enhancer of the BCG vaccine, functioning in part by modulating macrophage ab...

  4. BCG-Induced Dendritic Cell Responses and Suppression of Interleukin-5 Production from T Cells in Atopic Asthmatics

    OpenAIRE

    Choi, Inseon S.; Lin, Xiang-Hua; Koh, Young-Ah; Cui, Yong

    2008-01-01

    Bacille Calmette-Guérin (BCG) induces potent Th1 responses with the help of interleukin (IL)-10 and IL-12 released from dendritic cells (DCs), and suppresses Th2-associated allergic reactions. However, there are still some controversies on therapeutic effects of BCG in asthmatics. This study investigated whether BCG administration to DCs suppresses IL-5 production from T cells in atopic asthmatics. DCs derived from peripheral blood of subjects were cultured with or without BCG and Dermatophag...

  5. Oral Polio Vaccine Influences the Immune Response to BCG Vaccination. A Natural Experiment

    DEFF Research Database (Denmark)

    Sartono, E.; Lisse, I.M.; Terveer, E.M.; van de Sande, P.J.M.; Whittle, H.; Fisker, Bent; Roth, A.; Aaby, Peter; Yazdanbakhsh, M.; Benn, Christine Stabell

    2010-01-01

    BCG scar (0.95 (0.91-1.00), p = 0.057)). Among children with a scar, OPV was associated with reduced scar size, the regression coefficient being -0.24 (-0.43-0.05), p = 0.012. Conclusions: This study is the first to address the consequences for the immune response to BCG of simultaneous administration...

  6. Genome Sequence of Mycobacterium bovis BCG Moreau, the Brazilian Vaccine Strain against Tuberculosis

    OpenAIRE

    Gomes, Leonardo H. F.; Otto, Thomas D; Vasconcellos, Érico A.; Ferrão, Patrícia M.; Maia, Renata M.; Moreira, Aline S.; Ferreira, Marcelo A.; Castello-Branco, Luiz R. R.; Degrave, Wim M.; Mendonça-Lima, Leila

    2011-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only vaccine available against tuberculosis, and the strains used worldwide represent a family of daughter strains with distinct genotypic characteristics. Here we report the complete genome sequence of M. bovis BCG Moreau, the strain in continuous use in Brazil for vaccine production since the 1920s.

  7. Uptake of newly introduced universal BCG vaccination in newborns.

    LENUS (Irish Health Repository)

    Braima, O

    2012-01-31

    Universal neonatal BCG vaccination was discontinued in Cork in 1972. Following an outbreak of TB in 2 creches in the HSE South, a universal BCG vaccination program was re-introduced in October 2008. The aim of this study was to determine the vaccination process (in-hospital and community) and the in-hospital uptake of the vaccine. Following informed parental consent, babies of birth weight > 2.5 Kg were eligible for in-hospital vaccination if they were not: febrile, jaundiced on phototherapy, on antibiotics and if not born to HIV- positive mothers. Parents of babies not vaccinated in-hospital were asked to book an appointment in either of the 2 Cork community clinics. The immunisation nurse collected data on BCG vaccination, prospectively. This study examined vaccination uptakes in-hospital and community over a 6 month period (October 2008 to March 2009). There were 4018 deliveries during the study period. In-hospital consent was declined in only 16 babies (<1%) while the in-hospital vaccination uptake was 80% of total liv births. Although 635 newborns were admitted to the NICU, only 46 (8%) were vaccinated while in the NICU. At least 48% of planned community vaccination has been achieved to date. In conclusion, in-hospital consent was almost universal and vaccination uptake was satisfactory. NICU exclusion criteria accounted for a significant proportion of non-vaccination in-hospital. These criteria need to be readdressed considering that all premature babies are given other routine newborn vaccines at 2 months of age, regardless of weight.

  8. Uptake of newly introduced universal BCG vaccination in newborns.

    LENUS (Irish Health Repository)

    Braima, O

    2010-06-01

    Universal neonatal BCG vaccination was discontinued in Cork in 1972. Following an outbreak of TB in 2 creches in the HSE South, a universal BCG vaccination program was re-introduced in October 2008. The aim of this study was to determine the vaccination process (in-hospital and community) and the in-hospital uptake of the vaccine. Following informed parental consent, babies of birth weight > 2.5 Kg were eligible for in-hospital vaccination if they were not: febrile, jaundiced on phototherapy, on antibiotics and if not born to HIV- positive mothers. Parents of babies not vaccinated in-hospital were asked to book an appointment in either of the 2 Cork community clinics. The immunisation nurse collected data on BCG vaccination, prospectively. This study examined vaccination uptakes in-hospital and community over a 6 month period (October 2008 to March 2009). There were 4018 deliveries during the study period. In-hospital consent was declined in only 16 babies (<1%) while the in-hospital vaccination uptake was 80% of total liv births. Although 635 newborns were admitted to the NICU, only 46 (8%) were vaccinated while in the NICU. At least 48% of planned community vaccination has been achieved to date. In conclusion, in-hospital consent was almost universal and vaccination uptake was satisfactory. NICU exclusion criteria accounted for a significant proportion of non-vaccination in-hospital. These criteria need to be readdressed considering that all premature babies are given other routine newborn vaccines at 2 months of age, regardless of weight.

  9. Biochemical characterization of the maltokinase from Mycobacterium bovis BCG

    Directory of Open Access Journals (Sweden)

    Lamosa Pedro

    2010-05-01

    Full Text Available Abstract Background Maltose-1-phosphate was detected in Mycobacterium bovis BCG extracts in the 1960's but a maltose-1-phosphate synthetase (maltokinase, Mak was only much later purified from Actinoplanes missouriensis, allowing the identification of the mak gene. Recently, this metabolite was proposed to be the intermediate in a pathway linking trehalose with the synthesis of glycogen in M. smegmatis. Although the M. tuberculosis H37Rv mak gene (Rv0127 was considered essential for growth, no mycobacterial Mak has, to date, been characterized. Results The sequence of the Mak from M. bovis BCG was identical to that from M. tuberculosis strains (99-100% amino acid identity. The enzyme was dependent on maltose and ATP, although GTP and UTP could be used to produce maltose-1-phosphate, which we identified by TLC and characterized by NMR. The Km for maltose was 2.52 ± 0.40 mM and 0.74 ± 0.12 mM for ATP; the Vmax was 21.05 ± 0.89 μmol/min.mg-1. Divalent cations were required for activity and Mg2+ was the best activator. The enzyme was a monomer in solution, had maximal activity at 60°C, between pH 7 and 9 (at 37°C and was unstable on ice and upon freeze/thawing. The addition of 50 mM NaCl markedly enhanced Mak stability. Conclusions The unknown role of maltokinases in mycobacterial metabolism and the lack of biochemical data led us to express the mak gene from M. bovis BCG for biochemical characterization. This is the first mycobacterial Mak to be characterized and its properties represent essential knowledge towards deeper understanding of mycobacterial physiology. Since Mak may be a potential drug target in M. tuberculosis, its high-level production and purification in bioactive form provide important tools for further functional and structural studies.

  10. Code system BCG for gamma-ray skyshine calculation

    International Nuclear Information System (INIS)

    A code system BCG has been developed for calculating conveniently and efficiently gamma-ray skyshine doses using the transport calculation codes ANISN and DOT and the point-kernel calculation codes G-33 and SPAN. To simplify the input forms to the system, the forms for these codes are unified, twelve geometric patterns are introduced to give material regions, and standard data are available as a library. To treat complex arrangements of source and shield, it is further possible to use successively the code such that the results from one code may be used as input data to the same or other code. (author)

  11. Construction of EGFP-tagged rBCG of E.tenella and distribution in chickens

    Institute of Scientific and Technical Information of China (English)

    WANG QiuYue; LI JianHua; ZHANG XiChen; LIU ChengWu; CAO LiLi; REN KeYan; GONG PengTao; CAI YaNan

    2009-01-01

    Chicken coccidiosis is a major parasitic disease with substantial economic burden to the poultry in-dustry. Enhanced green fluorescent protein (EGFP) tagged recombinant Bacille Calmette-Guerin (rBCG), as a fusion protein with coccidian rhomboid antigen was constructed to track rBCG in vivo in chickens in this study. Immunization of chickens with one dose of rBCG pMV361-Rho/EGFP induced humoral immune response. The colonization of rBCG in liver, spleen, lung, kidney and caecum was observed by laser confocal microscopy. Real-time quantitative RT-PCR showed s rise expression level of rhomboid protein on the 7th day and a peak on the 14th day and disappearance on the 28th day after immunization. These results have significant implications for the development of rBCG vaccines against avian coccidiosis.

  12. Adverse effects of BCG vaccine 1173 P2 in Iran: A meta-analysis

    Science.gov (United States)

    Mostaan, Saied; Yazdanpanah, Bahador; Moukhah, Rasool; Hozouri, Hamid Reza; Rostami, Manouchehr; Khorashadizadeh, Mohsen; Zerehsaz, Javad; Mahabadi, Ramin Pirhajati; Saadi, Arya; Khanahmad, Hossein; Pooya, Mohammad

    2016-01-01

    Although in the last two decades the World Health Organization (WHO) has introduced tuberculosis as “a threat to global”, the vaccination with the Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the only way for the prevention of this fatal infectious disease. Despite of the efficacy of BCG vaccine especially against infants’ meningitis, it has still some limitations due to a variety of adverse effects. Many studies have evaluated the side effects of different strains of BCG vaccines in different countries. In Iran, some studies have been done so far to evaluate the adverse effects of 1173 P2 strain which is used for BCG vaccination. Each of these studies have used different standardization and sampling methods. This review will survey all studies that have been published about adverse effects of 1173 P2 strain of BCG vaccine in Iran using data mining methods.

  13. Construction of EGFP-tagged rBCG of E.tenella and distribution in chickens

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Chicken coccidiosis is a major parasitic disease with substantial economic burden to the poultry industry.Enhanced green fluorescent protein(EGFP) tagged recombinant Bacille Calmette-Guerin(rBCG),as a fusion protein with coccidian rhomboid antigen was constructed to track rBCG in vivo in chickens in this study.Immunization of chickens with one dose of rBCG pMV361-Rho/EGFP induced humoral immune response.The colonization of rBCG in liver,spleen,lung,kidney and caecum was observed by laser confocal microscopy.Real-time quantitative RT-PCR showed a rise expression level of rhomboid protein on the 7th day and a peak on the 14th day and disappearance on the 28th day after immunization.These results have significant implications for the development of rBCG vaccines against avian coccidiosis.

  14. Effect of revaccination with BCG in early childhood on mortality: randomised trial in Guinea-Bissau

    DEFF Research Database (Denmark)

    Roth, A.E.; Benn, Christine Stabell; Ravn, H.;

    2010-01-01

    inhabitants. Participants 2871 children aged 19 months to 5 years with low or no reactivity to tuberculin and who were not severely sick on the day of enrolment. Intervention BCG vaccination or no vaccination (control). Main outcome measure Hazard ratios for mortality. Results 77 children died during follow......-up. Compared with controls, the BCG revaccinated children had a hazard ratio of 1.20 (95% confidence interval 0.77 to 1.89). Two hundred and fifty children were admitted to hospital for the first time between enrolment and the end of the study, with an incidence rate ratio for BCG revaccinated children versus...... controls of 1.04 (0.81 to 1.33). The trial was stopped prematurely because of a cluster of deaths in the BCG arm of the study. This increase in mortality occurred at a time when many children had received missing vaccinations or vitamin A or iron supplementation; the hazard ratio for BCG revaccinated...

  15. Skirtingu laiku BCG vakcinomis skiepytų vaikų tuberkulino reakcijos ikimokykliniu laikotarpiu

    OpenAIRE

    Sučilienė, Elena

    2010-01-01

    Disertacijos objektas: įvairių BCG skiepijimo režimų įtaka tuberkulino reakcijos išraiškai, vietinei BCG žymei, specifinei serologijai, alergijos klinikai vaikams iki 6 m. Tyrime dalyvavo 509 vaikai, vakcinuoti įprasta arba pusine BCG vakcinos doze naujagimio ar 3 mėn. amžiaus. Jiems 3 mėn. po BCG vakcinacijos, 1, 2 ir 6 m. atliktas tuberkulino mėginys, įvertintas BCG randelis, ištirti specifiniai antikūnai kraujo serume, įvertintos alerginės būklės. Disertacijos išvadose konstatuojama, kad 3...

  16. Immunomodulatory effects of recombinant BCG expressing pertussis toxin on TNF-alpha and IL-10 in a bladder cancer model

    Directory of Open Access Journals (Sweden)

    Ramos Kátia L

    2008-11-01

    Full Text Available Abstract Background Since successful treatment of superficial bladder cancer with BCG requires proper induction of Th1 immunity, we have developed a rBCG-S1PT strain that induced a stronger cellular immune response than BCG. This preclinical study was designed to compare the modulatory effects of BCG and rBCG-S1PT on bladder TNF-α and IL-10 expression and to evaluate antitumour activity. Methods For Experiment I, the MB49 bladder cancer cell line was used in C57BL/6 mice. Chemical cauterization of the bladder was performed to promote intravesical tumor implantation. Mice were treated by intravesical instillation with BCG, rBCG-S1PT or PBS once a week for four weeks. After 35 days the bladders were removed and weighed. TNF-〈 and IL-10 cytokine responses were measured by qPCR. Experiment II was performed in the same manner as Experiment I, except the animals were not challenged with MB49 tumor cells. Results: rBCG-S1PT immunotherapy resulted in bladder weight reduction, compared to the BCG and control group. There were increases in TNF-α in the BCG-treated group, as well as increases in TNF-α and IL-10 mRNA in the rBCG-S1PT group. Conclusion These data indicate a significant reduction of bladder tumor volume for the rBCG group, compared to the BCG and PBS groups. This suggests that rBCG could be a useful substitute for wild-type BCG and that the potential modulation between TNF-α and IL-10 cytokine productions may have therapeutic value.

  17. Twin SMBH candidates in the BCG of RBS 797

    CERN Document Server

    Gitti, Myriam; Giovannini, Gabriele; Feretti, Luigina; Liuzzo, Elisabetta

    2015-01-01

    The radio-loud BCG at the center of the cool core cluster RBS 797 is known to exhibit a misalignment of its 5 GHz radio emission observed at different VLA resolutions, with the innermost kpc-scale jets being almost orthogonal to the radio lobes which extends for tens of kpc filling the X-ray cavities seen by Chandra. The different radio directions may be caused by rapid jet reorientation due to interaction with a secondary supermassive black hole (SMBH), or to the presence of two AGN, probably in a merging phase, which are emitting radio jets in different directions. We present the results of new 5 GHz observations performed with the EVN in May 2013. In particular, we detected two compact radio components, with a projected separation of 77 pc. We discuss two possible scenarios for the origin and nature of the EVN double source, showing that both interpretations are consistent with the presence of a SMBH binary system in the BCG of RBS 797.

  18. Cosmological Constraints From SDSS MaxBCG Cluster Abundances

    International Nuclear Information System (INIS)

    We perform a maximum likelihood analysis of the cluster abundance measured in the SDSS using the maxBCG cluster finding algorithm. Our analysis is aimed at constraining the power spectrum normalization σ8, and assumes flat cosmologies with a scale invariant spectrum, massless neutrinos, and CMB and supernova priors (Omega)mh2 = 0.128 ± 0.01 and h = 0.72 ± 0.05 respectively. Following the method described in the companion paper Rozo et al. (2007), we derive σ8 = 0.92 ± 0.10 (1σ) after marginalizing over all major systematic uncertainties. We place strong lower limits on the normalization, σ8 > 0.76 (95% CL) (> 0.68 at 99% CL). We also find that our analysis favors relatively low values for the slope of the Halo Occupation Distribution (HOD), α = 0.83 ± 0.06. The uncertainties of these determinations will substantially improve upon completion of an ongoing campaign to estimate dynamical, weak lensing, and X-ray cluster masses in the SDSS maxBCG cluster sample

  19. Evaluation of two different dendritic cell preparations with BCG reactivity

    Directory of Open Access Journals (Sweden)

    Fol Marek

    2016-01-01

    Full Text Available Dendritic cells (DCs play a key-role in the immune response against intracellular bacterial pathogens, including mycobacteria. Monocyte-derived dendritic cells (MoDCs are considered to behave as inflammatory cell populations. Different immunomagnetic methods (positive and negative can be used to purify monocytes before their in vitro differentiation and their culture behavior can be expected to be different. In this study we evaluated the reactivity of two dendritic cell populations towards the Bacillus Calmette-Guérin (BCG antigen. Monocytes were obtained from the blood of healthy donors, using positive and negative immunomagnetic separation methods. The expression of DC-SIGN, CD86, CD80, HLA-DR and CD40 on MoDCs was estimated by flow cytometry. The level of IL-12p70, IL-10 and TNF-α was measured by ELISA. Neither of the tested methods affected the surface marker expression of DCs. No significant alteration in immunological response, measured by cytokine production, was noted either. After BCG stimulation, the absence of IL-12, but the IL-23 production was observed in both cell preparations. Positive and negative magnetic separation methods are effective techniques to optimize the preparation of monocytes as the source of MoDCs for potential clinical application.

  20. Induction of Unconventional T Cells by a Mutant Mycobacterium bovis BCG Strain Formulated in Cationic Liposomes Correlates with Protection against Mycobacterium tuberculosis Infections of Immunocompromised Mice.

    Science.gov (United States)

    Derrick, Steven C; Yabe, Idalia; Morris, Sheldon; Cowley, Siobhan

    2016-07-01

    Earlier studies aimed at defining protective immunity induced by Mycobacterium bovis BCG immunization have largely focused on the induction of antituberculosis CD4(+) and CD8(+) T cell responses. Here we describe a vaccine consisting of a BCGΔmmaA4 deletion mutant formulated in dimethyl dioctadecyl-ammonium bromide (DDA) with d-(+)-trehalose 6,6'-dibehenate (TDB) (DDA/TDB) adjuvant (A4/Adj) that protected TCRδ(-/-) mice depleted of CD4(+), CD8(+), and NK1.1(+) T cells against an aerosol challenge with M. tuberculosis These mice were significantly protected relative to mice immunized with a nonadjuvanted BCGΔmmaA4 (BCG-A4) mutant and nonvaccinated controls at 2 months and 9 months postvaccination. In the absence of all T cells following treatment with anti-Thy1.2 antibody, the immunized mice lost the ability to control the infection. These results indicate that an unconventional T cell population was mediating protection in the absence of CD4(+), CD8(+), NK1.1(+), and TCRγδ T cells and could exhibit memory. Focusing on CD4(-) CD8(-) double-negative (DN) T cells, we found that these cells accumulated in the lungs postchallenge significantly more in A4/Adj-immunized mice and induced significantly greater frequencies of pulmonary gamma interferon (IFN-γ)-producing cells than were seen in the nonvaccinated or nonadjuvanted BCG control groups. Moreover, pulmonary DN T cells from the A4/Adj group exhibited significantly higher IFN-γ integrated median fluorescence intensity (iMFI) values than were seen in the control groups. We also showed that enriched DN T cells from mice immunized with A4/Adj could control mycobacterial growth in vitro significantly better than naive whole-spleen cells. These results suggest that formulating BCG in DDA/TDB adjuvant confers superior protection in immunocompromised mice and likely involves the induction of long-lived memory DN T cells. PMID:27226281

  1. Active Mycobacterium Infection Due to Intramuscular BCG Administration Following Multi-Steps Medication Errors

    Directory of Open Access Journals (Sweden)

    MohammadReza Rafati

    2015-10-01

    Full Text Available Bacillus Calmette-Guérin (BCG is indicated for treatment of primary or relapsing flat urothelial cell carcinoma in situ (CIS of the urinary bladder. Disseminated infectious complications occasionally occur due to BCG as a vaccine and intravesical therapy.  Intramuscular (IM or Intravenous (IV administrations of BCG are rare medication errors which are more probable to produce systemic infections. This report presents 13 years old case that several steps medication errors occurred consequently from physician handwriting, pharmacy dispensing, nursing administration and patient family. The physician wrote βHCG instead of HCG in the prescription. βHCG was read as BCG by the pharmacy staff and 6 vials of intravesical BCG were administered IM twice a week for 3 consecutive weeks. The patient experienced fever and chills after each injection, but he was admitted 2 months after first IM administration of BCG with fever and pancytopenia. Unfortunately four month after using drug, during second admission duo to cellulitis at the sites of BCG injection the physicians diagnosed the medication error. Using handwritten prescription and inappropriate abbreviations, spending inadequate time for taking a brief medical history in pharmacy, lack of verifying name, dose and wrote before medication administration and lack of considering medication error as an important differential diagnosis had roles to occur this multi-steps medication error.

  2. A Point Mutation in the mma3 Gene Is Responsible for Impaired Methoxymycolic Acid Production in Mycobacterium bovis BCG Strains Obtained after 1927

    OpenAIRE

    Behr, Marcel A.; Schroeder, Benjamin G.; Brinkman, Jacquelyn N.; Slayden, Richard A.; Barry, Clifton E.

    2000-01-01

    BCG vaccines are substrains of Mycobacterium bovis derived by attenuation in vitro. After the original attenuation (1908 to 1921), BCG strains were maintained by serial propagation in different BCG laboratories (1921 to 1961). As a result, various BCG substrains developed which are now known to differ in a number of genetic and phenotypic properties. However, to date, none of these differences has permitted a direct phenotype-genotype link. Since BCG strains differ in their abilities to synth...

  3. Enhanced and Enduring Protection against Tuberculosis by Recombinant BCG-Ag85C and Its Association with Modulation of Cytokine Profile in Lung

    OpenAIRE

    Jain, Ruchi; Dey, Bappaditya; Dhar, Neeraj; Rao, Vivek; Singh, Ramandeep; Gupta, Umesh D.; Katoch, V. M.; Ramanathan, V. D.; Tyagi, Anil K.

    2008-01-01

    Background The variable efficacy (0–80%) of Mycobacterium bovis Bacille Calmette Guréin (BCG) vaccine against adult tuberculosis (TB) necessitates development of alternative vaccine candidates. Development of recombinant BCG (rBCG) over-expressing promising immunodominant antigens of M. tuberculosis represents one of the potential approaches for the development of vaccines against TB. Methods/Principal Findings A recombinant strain of BCG - rBCG85C, over expressing the antigen 85C, a secretor...

  4. Effect of BCG vaccination on the frequency of 90Sr-induced osteosarcoma development in rats

    International Nuclear Information System (INIS)

    Using BCG vaccinated white rats of no breed the frequency of the development of induced osteosarcomas has been determined. It is shown that BCG injection of 5 mg per animal leads to changes in the frequency of the development of neoplasms and their multiplicity only in males which have been vaccinated 20 days before sup(90)Sr injection. The BCG dose increase up to 10 mg per animal in case of injection 10 days prior to sup(90)Sr administering has been accompanied by the suppression of the tumoral process independently of sex of experimental animals

  5. Assessment of immune response to repeat stimulation with BCG vaccine using in vitro PBMC model

    OpenAIRE

    Kashyap, Rajpal S; Husain, Aliabbas A.; Morey, Shweta H; Panchbhai, Milind S.; Deshpande, Poonam S; Purohit, Hemant J.; Taori, Girdhar M.; Daginawala, Hatim F.

    2010-01-01

    Background Tuberculosis (TB) is one of the most prevalent cause of death due to a single pathogen. Bacillus Calmette Guérin (BCG) is the only vaccine available for clinical use that protects against miliary TB; however, this vaccine has shown variable levels of efficacy against pulmonary TB. In India, a single dose of BCG vaccine is given and there are few countries where repeated doses of BCG are given. The incidence of TB in India is very high inspite of primary vaccination in neonatal peri...

  6. Recombinant Mycobacterium bovis BCG secreting functional interleukin-2 enhances gamma interferon production by splenocytes.

    OpenAIRE

    O'Donnell, M A; Aldovini, A; Duda, R B; Yang, H; Szilvasi, A; Young, R A; DeWolf, W C

    1994-01-01

    Mycobacterium bovis BCG was genetically engineered to express and secrete mouse interleukin-2 (IL-2) and rat IL-2. Genes encoding IL-2 were inserted into an Escherichia coli-BCG shuttle plasmid under the control of the BCG HSP60 promoter. To facilitate study of proteins produced in this system, the IL-2 gene product was expressed (i) alone, (ii) with the mycobacterial alpha-antigen secretion signal sequence at the amino terminus, (iii) with an influenza virus hemagglutinin epitope tag at the ...

  7. A COMBINED FULL-WAVE BCG-FFT METHOD FOR RADIATION OF MICROSTRIP ANTENNA ARRAYS

    Institute of Scientific and Technical Information of China (English)

    Zhang Hou; Peng Hongli; Liu Qizhong; Yin Yingzeng; Gong Shuxi

    2001-01-01

    A method of combining BiConjugate Gradient(BCG) with Fast Fourier Transform(FFT) to analyze the radiation of microstrip antenna arrays is presented, where the spatially discrete BCG-FFT for analyzing microstrip structure is used and the del operators on Green's functions are transferred from the singular kernel to the expansion and testing functions. The resultant equations are solved by using BCG method in which the matrix-vector product is evaluated efficiently with FFT. The calculated patterns are in good agreement with the measured data.

  8. "A Study of Relation between BCG Scar and Atopy in Schoolchildren of Zanjan City "

    Directory of Open Access Journals (Sweden)

    Akefeh Ahmadiafshar

    2005-12-01

    Three hundred and three subjects had at least one of these disorders, which were diagnosed as atopy. There was reverse correlation between BCG scar and asthma (P=0.013, atopic dermatitis (P<0.01, and atopy (P<0.01. We did not find any association between the diameter of BCG scar and allergic rhinitis. Reverse correlation of asthma, atopic dermatitis and atopy with BCG scar are significant. This relied on history and symptoms of patients. Further studies with skin tests, measurements of total and specific IgE levels and spirometery are recommended.

  9. BCG and New Preventive Tuberculosis Vaccines: Implications for Healthcare Workers.

    Science.gov (United States)

    Hatherill, Mark; Scriba, Thomas J; Udwadia, Zarir F; Mullerpattan, Jai B; Hawkridge, Anthony; Mahomed, Hassan; Dye, Christopher

    2016-05-15

    Healthcare workers (HCWs) are at high risk of Mycobacterium tuberculosis (Mtb) infection and tuberculosis disease, but also play a crucial role in implementing healthcare. Preexposure tuberculosis vaccination, including revaccination with BCG, might benefit Mtb-uninfected HCWs, but most HCWs in tuberculosis-endemic countries are already sensitized to mycobacteria. A new postexposure tuberculosis vaccine offers greatest potential for protection, in the setting of repeated occupational Mtb exposure. Novel strategies for induction of mycobacteria-specific resident memory T cells in the lung by aerosol administration, or induction of T cells with inherent propensity for residing in mucosal sites, such as CD1-restricted T cells and mucosa-associated innate T cells, should be explored. The need for improved protection of HCWs against tuberculosis disease is clear. However, health systems in tuberculosis-endemic countries would need significantly improved occupational health structures to implement a screening and vaccination strategy for HCWs. PMID:27118856

  10. Antigen-Specific CD4 T Cells Are Induced after Intravesical BCG-Instillation Therapy in Patients with Bladder Cancer and Show Similar Cytokine Profiles as in Active Tuberculosis

    OpenAIRE

    Elsäßer, Julia; Janssen, Martin W.; Becker, Frank; Suttmann, Henrik; Schmitt, Kai; Sester, Urban; Stöckle, Michael; Sester, Martina

    2013-01-01

    Specific T cell immunity in patients with active tuberculosis is associated with a decrease in multifunctionality. However, it is unknown whether cytokine profiles differ in patients with primary infection and those with prior contact. We therefore used intravesical immunotherapy with attenuated live Bacille Calmette–Guérin (BCG) in patients with urothelial carcinoma as a model to characterise the induction of systemic immunity towards purified protein derivate (PPD) and to study whether cyto...

  11. Vaccination against M. tuberculosis – what next after BCG?

    Directory of Open Access Journals (Sweden)

    Marek Fol

    2011-01-01

    Full Text Available Tuberculosis (TB still remains a huge global health problem. An increase in TB has been observed in many parts of the world, especially in poor and densely populated sub-Saharan Africa and Asia. Tuberculosis affects not only the developing countries but also the relatively wealthy regions of Europe, particularly Eastern Europe, where drug-resistant mycobacterial strains are increasingly reported.Control of tuberculosis expansion is very difficult. It requires the long-term use of anti-mycobacterial drugs. Additionally, the HIV epidemic and the phenomenon of multi-drug resistance are assumed to be responsible for the increase in TB cases. Therefore the most reasonable form of anti-TB protection seems to be effective vaccination.At the beginning of the twentieth century the BCG vaccine was introduced into general use as the first and so far the only immune protector against tuberculosis. Now it is known that this vaccine is not powerful enough and induces protection at a relatively low level. Hence ongoing research on the development of a more powerful anti-mycobacterial vaccine is still needed. Many of the new formulations are in phase II or III of clinical trials and the results are promising. The search for new vaccines involves several strategies: modified virulence-attenuated [i]Mycobacterium tuberculosis[/i] strains, recombination of attenuated M. bovis BCG bacilli, immunogenic mycobacterial proteins and DNA encoding selected proteins as well as unrelated microorganisms used as carriers of mycobacterial antigens. The wide range of concepts is extremely important because new vaccines should serve for immunization of the broadest possible population, not only healthy individuals but also those who are immunocompromised.

  12. The use of directed evolution to create a stable and immunogenic recombinant BCG expressing a modified HIV-1 Gag antigen.

    Directory of Open Access Journals (Sweden)

    Rosamund Chapman

    Full Text Available Numerous features make Mycobacterium bovis BCG an attractive vaccine vector for HIV. It has a good safety profile, it elicits long-lasting cellular immune responses and in addition manufacturing costs are affordable. Despite these advantages it is often difficult to express viral antigens in BCG, which results in genetic instability and low immunogenicity. The aim of this study was to generate stable recombinant BCG (rBCG that express high levels of HIV antigens, by modification of the HIV genes. A directed evolution process was applied to recombinant mycobacteria that expressed HIV-1 Gag fused to the green fluorescent protein (GFP. Higher growth rates and increased GFP expression were selected for. Through this process a modified Gag antigen was selected. Recombinant BCG that expressed the modified Gag (BCG[pWB106] and BCG[pWB206] were more stable, produced higher levels of antigen and grew faster than those that expressed the unmodified Gag (BCG[pWB105]. The recombinant BCG that expressed the modified HIV-1 Gag induced 2 to 3 fold higher levels of Gag-specific CD4 T cells than those expressing the unmodified Gag (BCG[pWB105]. Mice primed with 10(7 CFU BCG[pWB206] and then boosted with MVA-Gag developed Gag-specific CD8 T cells with a frequency of 1343±17 SFU/10(6 splenocytes, 16 fold greater than the response induced with MVA-Gag alone. Levels of Gag-specific CD4 T cells were approximately 5 fold higher in mice primed with BCG[pWB206] and boosted with MVA-Gag than in those receiving the MVA-Gag boost alone. In addition mice vaccinated with BCG[pWB206] were protected from a surrogate vaccinia virus challenge.

  13. The use of directed evolution to create a stable and immunogenic recombinant BCG expressing a modified HIV-1 Gag antigen.

    Science.gov (United States)

    Chapman, Rosamund; Bourn, William R; Shephard, Enid; Stutz, Helen; Douglass, Nicola; Mgwebi, Thandi; Meyers, Ann; Chin'ombe, Nyasha; Williamson, Anna-Lise

    2014-01-01

    Numerous features make Mycobacterium bovis BCG an attractive vaccine vector for HIV. It has a good safety profile, it elicits long-lasting cellular immune responses and in addition manufacturing costs are affordable. Despite these advantages it is often difficult to express viral antigens in BCG, which results in genetic instability and low immunogenicity. The aim of this study was to generate stable recombinant BCG (rBCG) that express high levels of HIV antigens, by modification of the HIV genes. A directed evolution process was applied to recombinant mycobacteria that expressed HIV-1 Gag fused to the green fluorescent protein (GFP). Higher growth rates and increased GFP expression were selected for. Through this process a modified Gag antigen was selected. Recombinant BCG that expressed the modified Gag (BCG[pWB106] and BCG[pWB206]) were more stable, produced higher levels of antigen and grew faster than those that expressed the unmodified Gag (BCG[pWB105]). The recombinant BCG that expressed the modified HIV-1 Gag induced 2 to 3 fold higher levels of Gag-specific CD4 T cells than those expressing the unmodified Gag (BCG[pWB105]). Mice primed with 10(7) CFU BCG[pWB206] and then boosted with MVA-Gag developed Gag-specific CD8 T cells with a frequency of 1343±17 SFU/10(6) splenocytes, 16 fold greater than the response induced with MVA-Gag alone. Levels of Gag-specific CD4 T cells were approximately 5 fold higher in mice primed with BCG[pWB206] and boosted with MVA-Gag than in those receiving the MVA-Gag boost alone. In addition mice vaccinated with BCG[pWB206] were protected from a surrogate vaccinia virus challenge. PMID:25061753

  14. Role of a bacillus Calmette-Guérin fibronectin attachment protein in BCG-induced antitumor activity.

    Science.gov (United States)

    Zhao, W; Schorey, J S; Bong-Mastek, M; Ritchey, J; Brown, E J; Ratliff, T L

    2000-04-01

    Intravesical Mycobacterium bovis bacillus Calmette-Gu*erin (BCG) is the treatment of choice for superficial bladder cancer. Previous studies showed that attachment of BCG to fibronectin within the bladder was necessary for mediation of the antitumor response. Further studies identified a bacterial receptor, fibronectin attachment protein (FAP), as an important mediator of BCG attachment to fibronectin. In vitro studies showed that a stable BCG/fibronectin interaction was dependent on FAP binding to fibronectin; however, no role for FAP in the attachment of BCG in vivo has been characterized. We now report the cloning of the M. bovis BCG FAP (FAP-B) and demonstrate an important role for FAP in the in vivo attachment of BCG to the bladder wall and in the induction of BCG-mediated antitumor activity. The predicted amino acid sequence for FAP-B shows 61% and 71% homology, respectively, with Mycobacterium avium FAP (FAP-A) and Mycobacterium leprae FAP (FAP-L). Rabbit polyclonal antibodies against Mycobacterium vaccae FAP (FAP-V) reacted with all 3 recombinant FAP proteins on Western blots. Functional studies show FAP-B to bind fibronectin via the highly conserved attachment regions previously identified for FAP-A and FAP-L and also to competitively inhibit attachment of BCG to matrix fibronectin. In vivo studies show FAP to be a necessary protein for the stable attachment of BCG to the bladder wall. Moreover, stable binding of BCG via FAP was shown to be necessary for the expression of BCG-induced antitumor activity. Our results demonstrate a biological role for FAP in the mediation of BCG-induced antitumor activity. PMID:10728599

  15. The success and failure of BCG - implications for a novel tuberculosis vaccine.

    Science.gov (United States)

    Andersen, Peter; Doherty, T Mark

    2005-08-01

    Over the past 50 years, the Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine against tuberculosis (TB) has maintained its position as the world's most widely used vaccine, despite showing highly variable efficacy (0-80%) in different trials. The efficacy of BCG in adults is particularly poor in tropical and subtropical regions. Studies in animal models of TB, supported by data from clinical BCG trials in humans, indicate that this failure is related to pre-existing immune responses to antigens that are common to environmental mycobacteria and Mycobacterium tuberculosis. Here, we discuss the potential mechanisms behind the variation of BCG efficacy and their implications for an improved TB vaccination strategy. PMID:16012514

  16. Demonstrating Functional Equivalence of Pilot and Production Scale Freeze-Drying of BCG

    Science.gov (United States)

    ten Have, R.; Reubsaet, K.; van Herpen, P.; Kersten, G.; Amorij, J.-P.

    2016-01-01

    Process analytical technology (PAT)-tools were used to monitor freeze-drying of Bacille Calmette-Guérin (BCG) at pilot and production scale. Among the evaluated PAT-tools, there is the novel use of the vacuum valve open/close frequency for determining the endpoint of primary drying at production scale. The duration of primary drying, the BCG survival rate, and the residual moisture content (RMC) were evaluated using two different freeze-drying protocols and were found to be independent of the freeze-dryer scale evidencing functional equivalence. The absence of an effect of the freeze-dryer scale on the process underlines the feasibility of the pilot scale freeze-dryer for further BCG freeze-drying process optimization which may be carried out using a medium without BCG. PMID:26981867

  17. Vitamin A supplementation and BCG vaccination at birth may affect atopy in childhood

    DEFF Research Database (Denmark)

    Kiraly, N; Benn, Christine Stabell; Biering-Sørensen, S; Rodrigues, A; Jensen, K J; Ravn, H; Allen, K J; Aaby, Peter

    2013-01-01

    Recent evidence suggests that immunogenic interventions such as vaccines and micronutrients may affect atopic sensitization and atopic disease. We aimed to determine whether neonatal BCG vaccination, vitamin A supplementation and other vaccinations affect atopy in childhood....

  18. Genetic control of antibody responses induced by recombinant Mycobacterium bovis BCG expressing a foreign antigen.

    OpenAIRE

    Lagranderie, M; Lo-Man, R; Dériaud, E; Gicquel, B; Gheorghiu, M; Leclerc, C

    1997-01-01

    Recombinant Mycobacterium bovis BCG expressing foreign antigens represents a promising candidate for the development of future vaccines and was shown in several experimental models to induce protective immunity against bacterial or parasitic infections. Innate resistance to BCG infection is under genetic control and could modify the immune responses induced against an antigen delivered by such engineered microorganisms. To investigate this question, we analyzed the immune responses of various...

  19. Evolution of M. bovis BCG Vaccine: Is Niacin Production Still a Valid Biomarker?

    OpenAIRE

    Sarman Singh; Manoj Kumar; Pragati Singh

    2015-01-01

    BCG vaccine is usually considered to be safe though rarely serious complications have also been reported, often incriminating contamination of the seed strain with pathogenic Mycobacterium tuberculosis. In such circumstances, it becomes prudent to rule out the contamination of the vaccine seed. M. bovis BCG can be confirmed by the absence of nitrate reductase, negative niacin test, and resistance to pyrazinamide and cycloserine. Recently in India, some stocks were found to be niacin positive ...

  20. Mantoux test results and BCG vaccination status in TB-exposed children

    OpenAIRE

    Fadilah Harahap; Ridwan M. Daulay; Muhammad Ali; Wisman Dalimunthe; Rini Savitri Daulay

    2016-01-01

    Background Tuberculosis (TB) infection is highly prevalent in Indonesia. The source of transmission of TB to a child is usually via an adult with sputum smear-positive pulmonary tuberculosis. The Mantoux test is a diagnostic tool for tuberculosis infection. The BCG vaccine has been used for the prevention of TB, but its efficacy is still debated. Objective To assess for an association between Mantoux test results and BCG vaccination in children who had contact with adult pulmonary tuberculosi...

  1. Comparison of IFN-gamma responses to mycobacterial antigens as markers of response to BCG vaccination.

    Science.gov (United States)

    Weir, Rosemary E; Fine, Paul E M; Floyd, Sian; Stenson, Sally; Stanley, Carolynne; Branson, Keith; Britton, Warwick J; Huygen, Kris; Singh, Mahavir; Black, Gillian; Dockrell, Hazel M

    2008-01-01

    An increase in interferon-gamma (IFN-gamma) production to Mycobacterium tuberculosis purified protein derivative (Mtb PPD), as measured in the cultured diluted whole blood assay, is one indicator of a protective immune response to BCG vaccine. We have explored the potential for this assay to be improved by measuring IFN-gamma responses to more defined antigens of M. tuberculosis (short-term and mid-term culture filtrates, ESAT-6, 38 kDa), Mycobacterium bovis (MPB70), M. bovis BCG (Antigen 85) and Mycobacterium leprae (35 kDa), in UK teenagers before and 1 year after BCG vaccination (or no vaccination as controls). There was a significant increase in response to the culture filtrates post-vaccination, but this was no greater than that to Mtb PPD. Many teenagers responded to the purified antigens, in particular to Antigen 85, prior to vaccination, and BCG vaccination could only augment this pre-existing response to a limited extent; prior exposure to environmental mycobacteria can thus induce cross-reactive responses to antigens which complicate interpretation of in vitro assays of vaccine response. In contrast, ESAT-6 was recognised by only one teenager prior to vaccination, and, as expected, responses were not boosted by BCG. We therefore conclude that Mtb PPD is the antigen preparation of choice for assessing the immunogenicity of BCG vaccination. PMID:18277396

  2. [Sepsis and multiple organ failure after BCG instillation in bladder cancer].

    Science.gov (United States)

    Elmer, A; Bermes, U; Drath, L; Büscher, E; Viertel, A

    2004-12-01

    Local Bacillus Calmette-Guerin (BCG) immunotherapy is an effective and widely used treatment for superficial bladder carcino-ma. Local side effects are frequent, where-as systemic side effects are rare, but more serious. Systemic BCG infection as a life-threatening complication of intravesical BCG instillation should be suspected in any patient who presents with persistent fever after BCG instillation for bladder cancer.A 62-year-old patient had been treated with 6 intravesical BCG instillations for recurrent, multifocal bladder carcinoma.4 weeks after the last instillation, he presented with fever, malaise and scleral icterus. Laboratory tests revealed abnormal li-ver function tests, panzytopenia and signs of coagulation disorder. Bone marrow biopsy and liver biopsy showed non-caseating granulomas. Systemic BCG infection was suspected and antituberculous therapy combined with steroids was started. The patient developed severe sepsis and suffered from multiple organ failure. Despite partial improvement, the course was complicated by intracranial sinus thrombosis, and the patient died two month after admission. PMID:15645554

  3. [Sepsis and multiple organ failure after BCG-instillation for bladder cancer].

    Science.gov (United States)

    Elmer, A; Bermes, U; Drath, L; Büscher, E; Viertel, A

    2004-08-01

    Local Bacillus Calmette-Guérin (BCG) immunotherapy is an effective and widely used treatment for superficial bladder carcinoma. Local side effects are frequent, whereas systemic side effects are rare, but more serious. Systemic BCG infection as a life-threatening complication of intravesical BCG instillation should be suspected in any patient who presents with persistent fever after BCG instillation for bladder cancer. A 62-year-old patient had been treated with 6 intravesical BCG instillations for recurrent, multifocal bladder carcinoma. 4 weeks after the last instillation, he presented with fever, malaise and scleral icterus. Laboratory tests revealed abnormal liver function tests, panzytopenia and signs of coagulation disorder. Bone marrow biopsy and liver biopsy showed noncaseating granulomas. Systemic BCG infection was suspected and antituberculous therapy combined with steroids was started. The patient developed severe sepsis and suffered from multiple organ failure. Despite partial improvement, the course was complicated by intracranial sinus thrombosis, and the patient died two month after admission. PMID:15138643

  4. The immunological effects of oral polio vaccine provided with BCG vaccine at birth

    DEFF Research Database (Denmark)

    Jensen, Kristoffer Jarlov; Karkov, Hanne Sophie; Lund, Najaaraq; Andersen, Andreas; Eriksen, Helle Brander; Barbosa, Amarildo Gomes; Kantsø, Bjørn; Aaby, Peter; Benn, Christine Stabell

    2014-01-01

    BACKGROUND: Vaccines may have non-specific effects. An observational study from Guinea-Bissau suggested that oral polio vaccine at birth (OPV0) provided with Bacillus Calmette-Guérin (BCG) vaccine was associated with down-regulation of the immune response to BCG vaccine 6 weeks later. Based on the...... BCG alone at birth, and subsequently randomised to have a blood sample taken at 2, 4 or 6 weeks post-randomisation. Excreted levels of cytokines (IL-2, IL-5, IL-10, TNF-α and IFN-γ) were measured from whole blood in vitro stimulations with a panel of recall vaccine antigens (BCG, PPD, OPV), mitogen...... previous finding, we wanted to test our a priori hypothesis that OPV would dampen the immune response to BCG, and secondarily to test immune responses to other antigens. METHODS: The study was conducted at the Bandim Health Project in Guinea-Bissau in 2009-2010. Infants were randomised to OPV0+BCG versus...

  5. Factors predicting BCG immunization status in northern Nigeria: a behavioral-ecological perspective.

    Science.gov (United States)

    Babalola, Stella; Lawan, Umar

    2009-03-01

    This study examines the predictors of Bacille Calmette-Guérin (BCG) immunization status among infants in northern Nigeria using a behavioral-ecological model. The findings show only 37.3 percent of the children had received BCG vaccine, and reveal that BCG immunization status in northern Nigeria is influenced by multiple layers of factors, including child's characteristics, parental or household factors, community characteristics, vaccine supply and the policy environment. At the child's level, place of birth and ownership of an immunization card are the two most significant predictors. The parental and household predictors of BCG immunization status include maternal use of antenatal care, maternal knowledge about immunization, maternal exposure to child health information, social influence and paternal approval of immunization. Both the regularity of vaccine supply to the health facility and the state of residence are associated independently with BCG immunization status. These findings stress the need for interventions at multiple levels in order to increase BCG immunization status. PMID:19240190

  6. Comparative evaluation of booster efficacies of BCG, Ag85B, and Ag85B peptides based vaccines to boost BCG induced immunity in BALB/c mice: a pilot study

    OpenAIRE

    Husain, Aliabbas A.; Warke, Shubhangi R.; Kalorey, Dewanand R.; Daginawala, Hatim F.; Taori, Girdhar M.; Kashyap, Rajpal S

    2015-01-01

    Purpose In the present study booster efficacies of Ag85 B, Bacillus Calmette-Guerin (BCG), and Ag85B peptides were evaluated using prime boost regimes in BALB/c mice. Materials and Methods Mice were primed with BCG vaccine and subsequently boosted with Ag85B, BCG and cocktail of Ag85B peptides. Results Based on analysis of immune response it was observed mice boosted with Ag85B peptides showed significant (p < 0.001) cytokines levels (interferon γ, interleukin 12) and BCG specific antibodies ...

  7. Removing ballistocardiogram (BCG) artifact from full-scalp EEG acquired inside the MR scanner with Orthogonal Matching Pursuit (OMP)

    OpenAIRE

    Xia, Hongjing; Ruan, Dan; Cohen, Mark S.

    2014-01-01

    Ballistocardiogram (BCG) artifact remains a major challenge that renders electroencephalographic (EEG) signals hard to interpret in simultaneous EEG and functional MRI (fMRI) data acquisition. Here, we propose an integrated learning and inference approach that takes advantage of a commercial high-density EEG cap, to estimate the BCG contribution in noisy EEG recordings from inside the MR scanner. To estimate reliably the full-scalp BCG artifacts, a near-optimal subset (20 out of 256) of chann...

  8. Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates: two by two factorial randomised controlled trial

    OpenAIRE

    Benn, Christine Stabell; Fisker, Ane Bærent; Napirna, Bitiguida Mutna; Roth, Adam; Diness, Birgitte Rode; Lausch, Karen Rokkedal; Ravn, Henrik; Yazdanbakhsh, Maria; Rodrigues, Amabelia; Whittle, Hilton; Aaby, Peter

    2010-01-01

    Objective To investigate the effect of vitamin A supplementation and BCG vaccination at birth in low birthweight neonates. Design Randomised, placebo controlled, two by two factorial trial. Setting Bissau, Guinea-Bissau. Participants 1717 low birthweight neonates born at the national hospital. Intervention Neonates who weighed less than 2.5 kg were randomly assigned to 25 000 IU vitamin A or placebo, as well as to early BCG vaccine or the usual late BCG vaccine, and were followed until age 12...

  9. Intravesical BCG therapy in bladder carcinoma. Effect on cytotoxicity, IL-2 production and phenotype of peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Hermann, G G; Petersen, K R; Zeuthen, J; Steven, K

    1991-01-01

    The purpose of the study was to examine the effects of intravesical BCG treatment on the cytotoxicity, interleukin-2 (IL-2) production and distribution of the subsets of peripheral blood mononuclear cells (PBMC) in patients with carcinoma in situ of the bladder. Treatments were made in 6 patients...... during a conventional BCG treatment schedule. Four patients showed a complete response, one a partial response and one had a progressive disease after BCG treatment. Intravesical BCG did not induce significant changes in the cytotoxicity of PBMC. The distribution of NK-cells and T-cells also remained...

  10. Parenteral adenoviral boost enhances BCG induced protection, but not long term survival in a murine model of bovine TB.

    Science.gov (United States)

    Kaveh, Daryan A; Garcia-Pelayo, M Carmen; Webb, Paul R; Wooff, Esen E; Bachy, Véronique S; Hogarth, Philip J

    2016-07-25

    Boosting BCG using heterologous prime-boost represents a promising strategy for improved tuberculosis (TB) vaccines, and adenovirus (Ad) delivery is established as an efficacious boosting vehicle. Although studies demonstrate that intranasal administration of Ad boost to BCG offers optimal protection, this is not currently possible in cattle. Using Ad vaccine expressing the mycobacterial antigen TB10.4 (BCG/Ad-TB10.4), we demonstrate, parenteral boost of BCG immunised mice to induce specific CD8(+) IFN-γ producing T cells via synergistic priming of new epitopes. This induces significant improvement in pulmonary protection against Mycobacterium bovis over that provided by BCG when assessed in a standard 4week challenge model. However, in a stringent, year-long survival study, BCG/Ad-TB10.4 did not improve outcome over BCG, which we suggest may be due to the lack of additional memory cells (IL-2(+)) induced by boosting. These data indicate BCG-prime/parenteral-Ad-TB10.4-boost to be a promising candidate, but also highlight the need for further understanding of the mechanisms of T cell priming and associated memory using Ad delivery systems. That we were able to generate significant improvement in pulmonary protection above BCG with parenteral, rather than mucosal administration of boost vaccine is critical; suggesting that the generation of effective mucosal immunity is possible, without the risks and challenges of mucosal administration, but that further work to specifically enhance sustained protective immunity is required. PMID:27317453

  11. Early BCG vaccine to low-birth-weight infants and the effects on growth in the first year of life

    DEFF Research Database (Denmark)

    Biering-Sørensen, Sofie; Andersen, Andreas; Ravn, Henrik;

    2015-01-01

    . METHODS: Two-thousand three hundred forty-three LBW infants were randomly allocated 1:1 to "early BCG" (intervention group) or "late BCG" (current practice). Furthermore, a subgroup (N = 1717) were included in a two-by-two randomised trial in which they were additionally randomised 1:1 to vitamin A...... but not among boys (interaction between "early BCG" and sex: weight p = 0.03 and MUAC p = 0.04). This beneficial effect among girls was particularly seen among the largest infants weighing 2.0 kg or more at inclusion. CONCLUSION: Though BCG vaccination is not recommended to be given to LBW infants at...

  12. Vaccine-associated paralytic poliomyelitis and BCG-osis in an immigrant child with severe combined immunodeficiency syndrome - Texas, 2013.

    Science.gov (United States)

    Trimble, Robert; Atkins, Jane; Quigg, Troy C; Burns, Cara C; Wallace, Gregory S; Thomas, Mary; Mangla, Anil T; Infante, Anthony J

    2014-08-22

    Poliovirus transmission has been eliminated in most of the world through the use of inactivated poliovirus vaccine (IPV) and live, attenuated oral poliovirus vaccine (OPV). In the United States, use of OPV was discontinued by the year 2000 because of the potential for vaccine-associated paralytic polio (VAPP); an average of eight cases were reported each year in the United States during 1980-2000. Polio eradication efforts in other parts of the world continue to rely on OPV to take advantage of transmission of poliovirus vaccine strains to unvaccinated persons in the population, lower cost, and ease of administration. In 2013, an infant aged 7 months who recently immigrated to the United States from India was referred to a hospital in San Antonio, Texas. The infant had fever, an enlarging skin lesion in the deltoid region with axillary lymphadenopathy, decreased activity, and inability to bear weight on the left leg, progressing to paralysis of the left leg over a 6-week period. Recognition of lymphopenia on complete blood count led to immune evaluation, which revealed the presence of severe combined immunodeficiency syndrome (SCIDS), an inherited disorder. A history of OPV and bacille Calmette-Guérin (BCG) vaccination in India led to the diagnoses of VAPP and BCG-osis, which were confirmed microbiologically. This report demonstrates the importance of obtaining a comprehensive clinical history in a child who has recently immigrated to the United States, with recognition that differing vaccine practices in other countries might require additional consideration of potential etiologies. PMID:25144542

  13. Neonatal BCG vaccination of mice improves neurogenesis and behavior in early life.

    Science.gov (United States)

    Yang, Junhua; Qi, Fangfang; Gu, Huaiyu; Zou, Juntao; Yang, Yang; Yuan, Qunfang; Yao, Zhibin

    2016-01-01

    Bacillus Calmette-Guérin (BCG) is administered to neonates worldwide, but it is still unknown whether this neonatal vaccination affects brain development during early postnatal life, despite the close association of the immune system with the brain. Newborn C57BL/6 mice were injected subcutaneously with BCG or phosphate-buffered saline (PBS) and their mood status and spatial cognition were observed at four and eight weeks (w) old. The mice were also subjected to tests at 2 and 6 w to examine BCG's effects on neurogenesis, the hippocampal microglia phenotype and number, and the expression of hippocampal neuroimmune molecules and peripheral cytokines. The BCG-injected mice showed better behavioral performances at 4 w. We observed elevated neurogenesis, M2 microglial activation and a neurotrophic profile of neuroimmune molecules [more interferon (IFN)-γ, interleukin (IL)-4, transforming growth factor (TGF)-β, brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF)-1 and less tumor necrosis factor (TNF)-α and IL-1β] in the hippocampus of the 2-w-old BCG-mice. In the periphery, BCG induced a T helper (Th)-1 serum response. At the individual level, there were positive correlations between the serum IFN-γ/IL-4 ratio and the levels of neurotrophins and neurogenesis in the hippocampus. These findings suggest that neonatal BCG vaccination improved neurogenesis and mouse behavior in early life by affecting the neuroimmune milieu in the brain, which may be associated with a systemic Th1 bias. PMID:26536170

  14. Low Dose BCG Regimen in T1 Transitional Cell Carcinoma of the Bladder: Long Term Results

    International Nuclear Information System (INIS)

    BCG has been used for more than 30 years and is currently the most effective agent for non-muscle invasive bladder cancer therapy after transurethral resection. The high-grade T1 lesion treated by transurethral resection alone is reported to progress to muscle invasion in 30% to 50% of the patients. Until now, optimal treatment schedule and optimal dose have not been defined as the toxicity related to BCG therapy is significant. In this study we tried to evaluate the efficacy and toxicity of 60 mg intravesical BCG (Pasteur strain) therapy in patients with T1 transitional cell carcinoma of the bladder. Patients and Methods: From January 2000 till December 2007, 74 patients with single T1 transitional cell carcinoma (TCC) of the urinary bladder (grade 3 in 24 patients and grade 2 in 50 patients) were treated by complete transurethral resection followed by a 6-weeks course of 60 mg BCG intravesically. Follow-up ranged from 26- 96 months with median of 61 months. Results: Nine patients (12.1%) exhibited recurrence with muscle invasion after 6-18 months (5 with grade 3 tumors and 4 with grade 2), all were subjected to radical cystectomy and urine diversion. Whereas 19 patients (29.2%) showed recurrent T1 tumor after 16-45 months (7 with grade 3 tumors and 12 with grade 2) and were treated by TUR-T followed by a second 6-weeks course of 60 mg BCG intravesically. Recurrence index was 0.82/100 patients/month and the median tumor free period was 20 months. Regarding toxicity; irritative symptoms occurred in 24% of patients, fever in 9%, microscopic hematuria in 14%; which appeared to be significantly low when compared with the rates reported for higher doses of BCG. Conclusion: Intravesical therapy of 60 mg BCG is effective in prophylaxis against recurrence and progression of T1 TCC of the bladder. Decreasing the dose resulted

  15. [Rifampicin-resistant Mycobacterium bovis BCG strain isolated from an infant with NEMO mutation].

    Science.gov (United States)

    Çavuşoğlu, Cengiz; Edeer Karaca, Neslihan; Azarsız, Elif; Ulusoy, Ezgi; Kütükçüler, Necil

    2015-04-01

    It is well known that disseminated Mycobacterium bovis BCG infection is developed after BCG vaccination in infants with congenital cellular immune deficiencies such as mutations in genes along the interleukin (IL)-12/interferon (IFN)-γ pathway and mutations in nuclear factor-kB essential modulator (NEMO). In this report, a rifampicin-resistant M.bovis BCG strain isolated from an infant with NEMO defect was presented. An 8-month-old male infant with NEMO defect admitted to the pediatric outpatient clinic of our hospital with fever, generalized lymphadenopathy and hepatosplenomegaly. Microscopic examination of the smears prepared from lymph node and liver biopsy specimens revealed abundant amount (3+) of acid-fast bacilli (AFB). Rifampicin-susceptible Mycobacterium tuberculosis complex (MTC) was detected by real-time PCR (GeneXpert MTB/RIF; Cepheid, USA) in the samples. The growth of mycobacteria was determined on the 20th day of culture performed in MGIT960 system (Becton Dickinson, USA). The isolate was identified as M.bovis BCG by GenoType MTBC kit (Hain Lifescience, Germany) and defined as M.bovis BCG [SIT 482 (BOV_1)] by spoligotyping. In the primary anti-tuberculosis drug susceptibility test performed by MGIT960 system, the isolate was found susceptible to rifampicin (RIF), isoniazid (INH), streptomycin (STM) and ethambutol (EMB). Then anti-tuberculosis treatment was started to the patient. However, the patient at the age of 2 years, re-admitted to the hospital with the complaint of hepatosplenomegaly. Smear of spontaneously draining abscess material obtained from subcutaneous nodules revealed intensive AFB positivity (3+) once again. In the present instance RIF-resistant MTC was detected with GeneXpert system in the specimen. The growth of mycobacteria was determined on the 13th day of culture and isolate was identified as M.bovis BCG. The present isolate was found susceptible to INH, STM and EMB but resistant to RIF. A mutation in the rpoB gene (codon 531, S

  16. Immunogenic Properties of a BCG Adjuvanted Chitosan Nanoparticle-Based Dengue Vaccine in Human Dendritic Cells.

    Science.gov (United States)

    Hunsawong, Taweewun; Sunintaboon, Panya; Warit, Saradee; Thaisomboonsuk, Butsaya; Jarman, Richard G; Yoon, In-Kyu; Ubol, Sukathida; Fernandez, Stefan

    2015-09-01

    Dengue viruses (DENVs) are among the most rapidly and efficiently spreading arboviruses. WHO recently estimated that about half of the world's population is now at risk for DENV infection. There is no specific treatment or vaccine available to treat or prevent DENV infections. Here, we report the development of a novel dengue nanovaccine (DNV) composed of UV-inactivated DENV-2 (UVI-DENV) and Mycobacterium bovis Bacillus Calmette-Guerin cell wall components (BCG-CWCs) loaded into chitosan nanoparticles (CS-NPs). CS-NPs were prepared by an emulsion polymerization method prior to loading of the BCG-CWCs and UVI-DENV components. Using a scanning electron microscope and a zetasizer, DNV was determined to be of spherical shape with a diameter of 372.0 ± 11.2 nm in average and cationic surface properties. The loading efficacies of BCG-CWCs and UVI-DENV into the CS-NPs and BCG-CS-NPs were up to 97.2 and 98.4%, respectively. THP-1 cellular uptake of UVI-DENV present in the DNV was higher than soluble UVI-DENV alone. DNV stimulation of immature dendritic cells (iDCs) resulted in a significantly higher expression of DCs maturation markers (CD80, CD86 and HLA-DR) and induction of various cytokine and chemokine productions than in UVI-DENV-treated iDCs, suggesting a potential use of BCG- CS-NPs as adjuvant and delivery system for dengue vaccines. PMID:26394138

  17. Kinetics of cytokine profile in response to Mycobacterium bovis BCG and Streptococcus pyogenes activated cells

    Science.gov (United States)

    Verma, Vivek; Kumar, Parveen; Dhanda, Rakesh Singh; Yadav, Manisha

    2016-01-01

    The infection of epithelial cells is a necessary step for Mycobacterium bovis BCG dissemination, but the mechanism of mycobacterial epithelial interactions is not completely understood. Similarly, Streptococcus pyogenes is a strictly human pathogen that favorably colonizes the skin and the pharynx. Effective cytokine secretion is essential in order to fabricate a suitable inflammatory response against an infection. In this data article, the cytokine profile in BCG and S. pyogenes activated THP-1 cell line in media after the acute phase of infection by ELISA is described. The interleukin-8 level was increased in response to both BCG and S. pyogenes, but was quite prominent after 24 h and further increased upto 72 h post infection. On the other hand, an increase in IL-6 response to S. pyogenes was observed while there was no response to BCG even after 48 h of infection. A low level of TNF-α was detected upon BCG and S. pyogenes infection. PMID:27014727

  18. Evolution of M. bovis BCG Vaccine: Is Niacin Production Still a Valid Biomarker?

    Directory of Open Access Journals (Sweden)

    Sarman Singh

    2015-01-01

    Full Text Available BCG vaccine is usually considered to be safe though rarely serious complications have also been reported, often incriminating contamination of the seed strain with pathogenic Mycobacterium tuberculosis. In such circumstances, it becomes prudent to rule out the contamination of the vaccine seed. M. bovis BCG can be confirmed by the absence of nitrate reductase, negative niacin test, and resistance to pyrazinamide and cycloserine. Recently in India, some stocks were found to be niacin positive which led to a national controversy and closer of a vaccine production plant. This prompted us to write this review and the comparative biochemical and genotypic studies were carried out on the these contentious vaccine stocks at the Indian vaccine plant and other seeds and it was found that some BCG vaccine strains and even some strains of M. bovis with eugenic-growth characteristics mainly old laboratory strains may give a positive niacin reaction. Most probably, the repeated subcultures lead to undefined changes at the genetic level in these seed strains. These changing biological characteristics envisage reevaluation of biochemical characters of existing BCG vaccine seeds and framing of newer guidelines for manufacturing, production, safety, and effectiveness of BCG vaccine.

  19. Evolution of M. bovis BCG Vaccine: Is Niacin Production Still a Valid Biomarker?

    Science.gov (United States)

    Singh, Sarman; Kumar, Manoj; Singh, Pragati

    2015-01-01

    BCG vaccine is usually considered to be safe though rarely serious complications have also been reported, often incriminating contamination of the seed strain with pathogenic Mycobacterium tuberculosis. In such circumstances, it becomes prudent to rule out the contamination of the vaccine seed. M. bovis BCG can be confirmed by the absence of nitrate reductase, negative niacin test, and resistance to pyrazinamide and cycloserine. Recently in India, some stocks were found to be niacin positive which led to a national controversy and closer of a vaccine production plant. This prompted us to write this review and the comparative biochemical and genotypic studies were carried out on the these contentious vaccine stocks at the Indian vaccine plant and other seeds and it was found that some BCG vaccine strains and even some strains of M. bovis with eugenic-growth characteristics mainly old laboratory strains may give a positive niacin reaction. Most probably, the repeated subcultures lead to undefined changes at the genetic level in these seed strains. These changing biological characteristics envisage reevaluation of biochemical characters of existing BCG vaccine seeds and framing of newer guidelines for manufacturing, production, safety, and effectiveness of BCG vaccine. PMID:25694828

  20. Kinetics of cytokine profile in response to Mycobacterium bovis BCG and Streptococcus pyogenes activated cells.

    Science.gov (United States)

    Verma, Vivek; Kumar, Parveen; Dhanda, Rakesh Singh; Yadav, Manisha

    2016-06-01

    The infection of epithelial cells is a necessary step for Mycobacterium bovis BCG dissemination, but the mechanism of mycobacterial epithelial interactions is not completely understood. Similarly, Streptococcus pyogenes is a strictly human pathogen that favorably colonizes the skin and the pharynx. Effective cytokine secretion is essential in order to fabricate a suitable inflammatory response against an infection. In this data article, the cytokine profile in BCG and S. pyogenes activated THP-1 cell line in media after the acute phase of infection by ELISA is described. The interleukin-8 level was increased in response to both BCG and S. pyogenes, but was quite prominent after 24 h and further increased upto 72 h post infection. On the other hand, an increase in IL-6 response to S. pyogenes was observed while there was no response to BCG even after 48 h of infection. A low level of TNF-α was detected upon BCG and S. pyogenes infection. PMID:27014727

  1. Clinical features and outcome of eleven patients with disseminated Bacille Calmette-Guerin (BCG) infection

    International Nuclear Information System (INIS)

    Disseminated BCG infection is a very rare complication of BCG vaccination. This study presents 11 patients with such complication. The underlying disease in eight of the 11 patients was primary immunodeficiency. Seven of these had severe combined immune deficiency (SCID) and one had isolated T-cell defect. Of the three remaining patients, one was healthy, one was diagnosed with mucocutaneous candidiasis and the third was diagnosed with leukocytoclastic vasculitis. Cutaneous nodular lesion, persistent fever, hepatosplenomegaly and pulmonary symptoms were common presenting features. All but one patient received antituberculous treatment. Four of 11 patients died because of extensive BCG disease. Three of these had SCID and one had T-cell deficiency. Patients with SCID who survived had bone marrow transplantation in addition to antituberculous chemotherapy. We conclude that a family history of immunodeficiency should be sought and if suggestive, BCG vaccine should be deferred until the immune status of the baby is clarified. In addition, early diagnosis is important for successful outcome. Bone marrow transplant on an emergency basis is the treatment of choice in patients with SCID and disseminated BCG infection, as immune reconstitution is essential to control infection in these patients. (author)

  2. Variation of growth in the production of the BCG vaccine and the association with the immune response. An observational study within a randomised trial

    DEFF Research Database (Denmark)

    Biering-Sørensen, Sofie; Jensen, Kristoffer Jarlov; Aamand, Susanne Havn;

    2015-01-01

    delayed BCG, the manufacturer of the BCG vaccine experienced a period with relatively slow growth rate of the BCG. We investigated the association between growth rate of BCG when manufacturing the vaccine and its capability to induce immune responses in vivo and in vitro. METHODS: 1633 neonates were......INTRODUCTION: Bacille Calmette-Guérin (BCG) vaccine has beneficial non-specific effects on overall survival. After BCG vaccination, positive PPD response and scar formation are associated with increased survival. During a trial randomising low-birth-weight neonates to BCG at birth or the usual...... production of BCG vaccine may influence important immunological effects of the vaccine. TRIAL REGISTRATION: clinicaltrials.gov (NCT00625482)....

  3. Effect of the injection of an extract of Ascaris suum on macrophage activation during the early phase of Mycobacterium bovis BCG infection in C57Bl/6 mice

    Directory of Open Access Journals (Sweden)

    Ferreira A.P.

    1999-01-01

    Full Text Available Injection of an Ascaris suum extract (Asc affects both the humoral and cellular immune responses to unrelated antigens when it is co-administered with these antigens. In the present study we evaluated the effect of Asc on macrophage activation in the early phase of Mycobacterium bovis BCG (Pasteur strain TMCC 1173 infection in C57Bl/6 mice. C57Bl/6 mice were injected intraperitoneally (ip with 0.1 mg BCG (BCG group or BCG plus 1 mg Asc (BCG + Asc group. The peritoneal exudates were obtained at 2, 7 and 14 days after infection. The numbers of IFN-g-secreting cells were assessed by the ELISPOT assay. Nitric oxide (NO production was measured by the Griess method and by the evaluation of NADPH diaphorase activity in the peritoneal exudates. The administration of Asc extract increased NADPH diaphorase activity (2 days: control = 0, BCG = 7%, BCG + Asc = 13%, and Asc = 4%; 7 days: control = 4, BCG = 13%, BCG + Asc = 21%, and Asc = 4.5% and TNF-a levels (mean ± SD; 2 days: control = 0, BCG = 169 ± 13, BCG + Asc = 202 ± 37, and Asc = 0; 7 days: control = 0, BCG = 545 ± 15.5, BCG + Asc = 2206 ± 160.6, and Asc = 126 ± 26; 14 days: control = 10 ± 1.45, BCG = 9 ± 1.15, BCG + Asc = 126 ± 18, and Asc = 880 ± 47.67 pg/ml in the early phase of BCG infection. Low levels of NO production were detected at 2 and 7 days after BCG infection, increasing at 14 days (mean ± SD; 2 days: control = 0, BCG = 3.7 ± 1.59, BCG + Asc = 0.82 ± 0.005, Asc = 0.48 ± 0.33; 7 days: control = 0, BCG = 2.78 ± 1.54, BCG + Asc = 3.07 ± 1.05, Asc = 0; 14 days: control = 0, BCG = 9.05 ± 0.53, BCG + Asc = 9.61 ± 0.81, Asc = 10.5 ± 0.2 (2 x 106 cells/ml. Furthermore, we also observed that Asc co-injection induced a decrease of BCG-colony-forming units (CFU in the spleens of BCG-infected mice during the first week of infection (mean ± SD; 2 days: BCG = 1.13 ± 0.07 and BCG + Asc = 0.798 ± 0.305; 7 days: BCG = 1.375 ± 0.194 and BCG + Asc = 0.548 ± 0.0226; 14 days: BCG

  4. Combination therapy using intratumoral bacillus Calmette-Guerin (BCG) and vincristine in dogs with transmissible venereal tumours : therapeutic efficacy and histological changes : article

    OpenAIRE

    S. Mukaratirwa; S. Chitanga; T. Chimatira; C. Makuleke; S.T. Sayi; E. Bhebhe

    2009-01-01

    Therapeutic efficacy and histological changes after bacillus Calmette-Guerin (BCG), vincristine and BCG/vincristine combination therapy of canine transmissible venereal tumours (CTVT) were studied. Twenty dogs with naturally occurring CTVT in the progression stage were divided into 4 groups and treated with intratumoral BCG, vincristine, BCG/vincristine combination therapy or intratumoral buffered saline (control group). Tumour sizes were determined weekly and tumour response to therapy was a...

  5. The influence of BCG vaccine strain on mycobacteria-specific and non-specific immune responses in a prospective cohort of infants in Uganda

    OpenAIRE

    Anderson, Elizabeth J.; Webb, Emily L.; Mawa, Patrice A.; Kizza, Moses; Lyadda, Nancy; Nampijja, Margaret; Elliott, Alison M

    2012-01-01

    Background Globally, BCG vaccination varies in efficacy and has some non-specific protective effects. Previous studies comparing BCG strains have been small-scale, with few or no immunological outcomes and have compared TB-specific responses only. We aimed to evaluate both specific and non-specific immune responses to different strains of BCG within a large infant cohort and to evaluate further the relationship between BCG strain, scarring and cytokine responses. Methods Infants from the Ente...

  6. A Modified Bacillus Calmette-Guérin (BCG) Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence

    OpenAIRE

    Kernodle, Douglas S.; Cynamon, Michael H.; Gates, Hiriam O.; Alexandria D. Allen; Miriam Braunstein; Kyi-Toe Tham; Shoen, Carolyn M.; Michelle S. DeStefano; Hager, Cynthia C.

    2013-01-01

    Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune...

  7. Vaccination technique, PPD reaction and BCG scarring in a cohort of children born in Guinea-Bissau 2000-2002

    DEFF Research Database (Denmark)

    Roth, Adam Anders Edvin; Sodemann, Morten; Jensen, Henrik; Poulsen, Anja; Gustafson, Per; Gomes, Justino; Djana, Queba; Jakobsen, Marianne; Garly, May-Lill; Rodrigues, Amabelia; Aaby, Peter

    2005-01-01

    The rates of positive tuberculin skin test (TST) reactions and BCG scarring after BCG vaccination vary between studies and populations. Tuberculin reactivity and BCG scarring may be related to better child survival in low-income countries. We therefore studied determinants for TST reaction and......=2225) of age. In a subgroup of the children the vaccination technique was monitored by direct observation of post-vaccination wheal and route of administration. Three different types of BCG vaccine supplied by the local Extended Programme on Immunization were used. At 6 months of age the rate of PPD...... reactors (>1mm) after BCG vaccination was 25% and the rate of scarring was 89%. One BCG strain was associated with fewer PPD reactors (OR=0.54 (0.31-0.91)) and BCG scars (OR=0.13 (0.05-0.37)) and larger post-vaccination wheals produced more PPD reactions (OR 1.21 (95% CI 1.02-1.43)) and BCG scars (OR 1...

  8. BCG Vaccination as a Prevention Strategy, Threats and Benefits

    Directory of Open Access Journals (Sweden)

    Shirvani

    2016-04-01

    Full Text Available Context Tuberculosis is still one of the deadliest communicable diseases. Objectives Nine million people worldwide developed TB in 2013, and 1.5 million people died from it, 360000 of which were HIV positive. Although the disease is controllable by means of diagnostic and treatment measures, the death toll from the disease is still high, and efforts to combat it must be accelerated. Data Sources Data compiled from 202 countries in the Global Tuberculosis Report 2014 showed that TB is present in all regions of the world. Study Selection Higher numbers of tuberculosis cases were diagnosed in 2013 in comparison with previous reports, indicating that diagnoses and reports of new cases may be improved by stringent data collection. Data Extraction A special note to the 2014 report highlighted the progress of drug resistant TB during the last two decades. Results Worldwide, a proportion of new cases with multidrug-resistant TB (MDR-TB were reported at 3.5% in 2013 without a significant change compared with recent years. Interestingly, higher levels of resistance and poor treatment outcomes are of major concern in some parts of the world. Due to this concern, special attention is focused on prevention rather than treatment. On the other hand, the effectiveness of an existing vaccine (BCG is increasingly questionable. Conclusions It has the potential to cause disseminated infection, and an increasing number of immunocompromised patients prone to disease and the suboptimal preventive potency of this vaccine suggest the need for a global attempt to review its benefits and disadvantages.

  9. Use of BCG or levamisole as an adjunct to chemotherapy or radiotherapy in malignant lymphomas

    International Nuclear Information System (INIS)

    Non-specific immunomodulators including BCG or levamisole have been used as an adjunct to chemotherapy or radiotherapy in both Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). In early stage HD, BCG and levamisole failed to show any effect over the use of radiotherapy alone. In advanced stage HD, disease-free survival as well as delayed type hypersensitive (DTH) appeared to be better though not significantly, in patients receiving combination chemotherapy interspersed with BCG as compared to chemotherapy alone. Levamisole proved to be ineffective both in HD and NHL as an immuno-restorative agent. The present study indicates that non-specific immunotherapy in malignant lymphomas, administered during the induction phase of therapy may not have the desired beneficial effect. (author)

  10. BCG vaccine for immunotherapy in warts: is it really safe in a tuberculosis endemic area?

    Science.gov (United States)

    Daulatabad, Deepashree; Pandhi, Deepika; Singal, Archana

    2016-05-01

    Management of recurrent and or recalcitrant warts can be a therapeutic challenge and in such cases invoking body's own immunity may help to overcome the present episode and also prevent recurrences. Bacilli Calmette Geurin (BCG) immunotherapy has long been considered to be an effective and safe modality in such cases. We present a series of seven cases treated with BCG immunotherapy wherein a single dose of BCG caused regression of wart in 85.7% patients and complete resolution was evident in 28.6% patients. However, the development of adverse effects precluded any further dosages in four of seven (57.1%) patients. This raises serious concern on the safety of this therapeutic modality, especially in a population endemic to tuberculosis. PMID:26809285

  11. Optimal control on bladder cancer growth model with BCG immunotherapy and chemotherapy

    Science.gov (United States)

    Dewi, C.; Trisilowati

    2015-03-01

    In this paper, an optimal control model of the growth of bladder cancer with BCG (Basil Calmate Guerin) immunotherapy and chemotherapy is discussed. The purpose of this optimal control is to determine the number of BCG vaccine and drug should be given during treatment such that the growth of bladder cancer cells can be suppressed. Optimal control is obtained by applying Pontryagin principle. Furthermore, the optimal control problem is solved numerically using Forward-Backward Sweep method. Numerical simulations show the effectiveness of the vaccine and drug in controlling the growth of cancer cells. Hence, it can reduce the number of cancer cells that is not infected with BCG as well as minimize the cost of the treatment.

  12. How do parents make their decision about letting their child get a BCG vaccination?

    DEFF Research Database (Denmark)

    Thybo Pihl, Gitte; Ammentorp, Jette; Schmidt Jensen, Jane;

    interpretation of cases of illness and atopic diseases in their personal network and family to evaluate risk for their child to develop atopic diseases or get hospitalised. This lay epidemiologi forms the basis for their decision. Davison C, Frankel S, Davey Smith G. Inheriting heart trouble: the relevance of......Introduction: In a large prospective randomised clinical trial in Denmark we are testing the hypothesis that compared to non-BCG-vaccinated infants, infants who are BCG vaccinated at birth experience less hospitalisations, use less antibiotics, and develop less atopic disease in early childhood. My...... focus for this project is parents decision making and risk evaluation. I want to investigate how parents make their decision about letting their child get a BCG vaccination and how they evaluate the risk of side effects. Method: Before the clinical trial was started, we conducted 5 focus groups with...

  13. A complete sample of massive MaxBCG clusters for scaling relations

    Science.gov (United States)

    Sun, Ming

    2013-10-01

    Great progress on galaxy clusters has been made in the last several years with SZ and optical surveys. Some new puzzles also emerged and one of them is the mismatch between the stacked Planck SZ fluxes and the model expectations for the MaxBCG clusters. While previous studies regarding this puzzle require the calibration of the true mass and the standard pressure template, we bypass the intermediate steps to directly compare the pressure content derived from the X-ray data with the SZ flux, for massive MaxBCG clusters. This proposal requests XMM data for 9 clusters to complete a sample of 38 most massive MaxBCG clusters observed with either XMM or Chandra. The results will shed light on the mismatch puzzle and constrain the important scaling relations like Y_X - N_200 and Y_X - Y_SZ.

  14. Variation of growth in the production of the BCG vaccine and the association with the immune response. An observational study within a randomised trial

    NARCIS (Netherlands)

    Biering-Sorensen, S.; Jensen, K.J.; Aamand, S.H.; Blok, B.; Andersen, A.; Monteiro, I.; Netea, M.G.; Aaby, P.; Benn, C.S.; Haslov, K.R.

    2015-01-01

    INTRODUCTION: Bacille Calmette-Guerin (BCG) vaccine has beneficial non-specific effects on overall survival. After BCG vaccination, positive PPD response and scar formation are associated with increased survival. During a trial randomising low-birth-weight neonates to BCG at birth or the usual delay

  15. Heterologous Immunological Effects of Early BCG Vaccination in Low-Birth-Weight Infants in Guinea-Bissau

    DEFF Research Database (Denmark)

    Jensen, Kristoffer Jarlov; Larsen, Nanna; Biering-Sørensen, Sofie;

    2015-01-01

    -Bissau of early BCG vs the usual postponed BCG, a subgroup was bled 4 weeks after randomization. Levels of interleukin (IL)-1β, IL-5, IL-6, IL-10, IL-17, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were measured from whole-blood assays stimulated with innate agonists to Toll-like receptor (TLR)-2......BACKGROUND:  Bacillus Calmette-Guérin (BCG) seems to have beneficial nonspecific effects; early BCG vaccination of low-birth-weight (LBW) newborns reduces neonatal mortality by >40% due to prevention of primarily septicemia and pneumonia. METHODS:  Within a randomized trial in LBW infants in Guinea...... stimulation, particularly of the cytokines IL-1β, IL-6, TNF-α, and IFN-γ. CONCLUSION:  Four weeks after immunization, BCG-vaccinated infants have a significantly increased production of cytokines upon heterologous challenge, particularly T helper cell type 1 polarizing and typically monocyte-derived pro...

  16. Stable Expression of Lentiviral Antigens by Quality-Controlled Recombinant Mycobacterium bovis BCG Vectors.

    Science.gov (United States)

    Hart, Bryan E; Asrican, Rose; Lim, So-Yon; Sixsmith, Jaimie D; Lukose, Regy; Souther, Sommer J R; Rayasam, Swati D G; Saelens, Joseph W; Chen, Ching-Ju; Seay, Sarah A; Berney-Meyer, Linda; Magtanong, Leslie; Vermeul, Kim; Pajanirassa, Priyadharshini; Jimenez, Amanda E; Ng, Tony W; Tobin, David M; Porcelli, Steven A; Larsen, Michelle H; Schmitz, Joern E; Haynes, Barton F; Jacobs, William R; Lee, Sunhee; Frothingham, Richard

    2015-07-01

    The well-established safety profile of the tuberculosis vaccine strain, Mycobacterium bovis bacille Calmette-Guérin (BCG), makes it an attractive vehicle for heterologous expression of antigens from clinically relevant pathogens. However, successful generation of recombinant BCG strains possessing consistent insert expression has encountered challenges in stability. Here, we describe a method for the development of large recombinant BCG accession lots which stably express the lentiviral antigens, human immunodeficiency virus (HIV) gp120 and simian immunodeficiency virus (SIV) Gag, using selectable leucine auxotrophic complementation. Successful establishment of vaccine stability stems from stringent quality control criteria which not only screen for highly stable complemented BCG ΔleuCD transformants but also thoroughly characterize postproduction quality. These parameters include consistent production of correctly sized antigen, retention of sequence-pure plasmid DNA, freeze-thaw recovery, enumeration of CFU, and assessment of cellular aggregates. Importantly, these quality assurance procedures were indicative of overall vaccine stability, were predictive for successful antigen expression in subsequent passaging both in vitro and in vivo, and correlated with induction of immune responses in murine models. This study has yielded a quality-controlled BCG ΔleuCD vaccine expressing HIV gp120 that retained stable full-length expression after 10(24)-fold amplification in vitro and following 60 days of growth in mice. A second vaccine lot expressed full-length SIV Gag for >10(68)-fold amplification in vitro and induced potent antigen-specific T cell populations in vaccinated mice. Production of large, well-defined recombinant BCG ΔleuCD lots can allow confidence that vaccine materials for immunogenicity and protection studies are not negatively affected by instability or differences between freshly grown production batches. PMID:25924766

  17. Avaliação da resposta inflamatória hematológica em cascavéis (Crotalus durissus Linnaeus, 1758 inoculadas com BCG Assessment of blood inflammatory response in BCG stimulated rattlesnakes (Crotalus durissus Linnaeus, 1758

    Directory of Open Access Journals (Sweden)

    Wellington Bandeira da Silva

    2009-12-01

    grandes vacúolos. De forma geral, a inoculação de BCG em cascavéis desencadeia respostas inflamatórias hematológicas caracterizadas pela participação de trombócitos, granulócitos e azurófilos.The high demand for anti-venom production in response to the increased number of cases of snakebite envenomation highlights the importance of raising and breeding venomous snakes in captivity. Knowledge of types of venoms and anti-venoms is of great interest to public health. The maintenance of venomous serpents in captivity started in the early twentieth century, but still nowadays it is a challenge to manage and prevent diseases in captive fauna. Hematology is commonly used for general health assessment and illness detection. However, data on serpent blood analysis are still scarce. Alterations in hematological parameters were experimentally induced in rattlesnakes by the inoculation of BCG. Based on this, hemograms can be used as a health auxiliary diagnosis method for bacterial diseases in this species. In this study, blood samples were taken from 10 healthy specimens of rattlesnakes (Crotalus durissus born and bred in captivity in the Herpetological Division of Vital Brazil Institute. Animals were divided into two groups (group 1 and 2 with similar live weight and sex proportion, and were then inoculated subcutaneously with BCG (Bacillus Calmette-Guérin. Blood samples were taken before and after inoculation at three experimental times (days 3, 5 and 7 for group 1 and days 11, 17 and 21 for group 2. Hematological analysis was performed through semi-direct technique, blood samples were diluted in Natt and Herrick solution and smears were stained by Giemsa. Serpents from group 1 developed discrete anemia due to the inflammatory syndrome, and showed significant decrease of MCH and MCHC. Granulocytes were characterized by the presence of rough granules. The azurophils varied in shape and size and showed large amount of cytoplasmic vacuoles. The thrombocytopenia observed

  18. Demonstrating Functional Equivalence of Pilot and Production Scale Freeze-Drying of BCG

    OpenAIRE

    ten Have, R; Reubsaet, K.; van Herpen, P.; Kersten, G.; Amorij, J.-P.

    2016-01-01

    Process analytical technology (PAT)-tools were used to monitor freeze-drying of Bacille Calmette-Guérin (BCG) at pilot and production scale. Among the evaluated PAT-tools, there is the novel use of the vacuum valve open/close frequency for determining the endpoint of primary drying at production scale. The duration of primary drying, the BCG survival rate, and the residual moisture content (RMC) were evaluated using two different freeze-drying protocols and were found to be independent of the...

  19. Inhibition of TLR8 mediated signaling promotes BCG induced apoptosis in THP-1 cells.

    Science.gov (United States)

    Tang, Jun; Zhan, Lingjun; Qin, Chuan

    2016-04-01

    Apoptosis was considered as one of the important host defense mechanisms against mycobacteria infection. In macrophage, the main target cell of Mycobacterium tuberculosis, apoptosis after infection could help kill the bacillus inside and process the antigens for further presentation and proper immune response. Here, we identified a role of TLR8 during the apoptosis induced by Bacillus Calmette Guérin (BCG) infection in THP-1 cells. Knockdown TLR8 further increased the apoptosis induced by BCG infection, and this enhanced apoptosis was caspase-dependent. During this process, Erk1/2, JNK and NFκB pathways were negatively affected and contributed to the enhanced apoptosis. PMID:26657720

  20. The Ag85B protein of the BCG vaccine facilitates macrophage uptake but is dispensable for protection against aerosol Mycobacterium tuberculosis infection.

    Science.gov (United States)

    Prendergast, Kelly A; Counoupas, Claudio; Leotta, Lisa; Eto, Carolina; Bitter, Wilbert; Winter, Nathalie; Triccas, James A

    2016-05-17

    Defining the function and protective capacity of mycobacterial antigens is crucial for progression of tuberculosis (TB) vaccine candidates to clinical trials. The Ag85B protein is expressed by all pathogenic mycobacteria and is a component of multiple TB vaccines under evaluation in humans. In this report we examined the role of the BCG Ag85B protein in host cell interaction and vaccine-induced protection against virulent Mycobacterium tuberculosis infection. Ag85B was required for macrophage infection in vitro, as BCG deficient in Ag85B expression (BCG:(Δ85B)) was less able to infect RAW 264.7 macrophages compared to parental BCG, while an Ag85B-overexpressing BCG strain (BCG:(oex85B)) demonstrated improved uptake. A similar pattern was observed in vivo after intradermal delivery to mice, with significantly less BCG:(Δ85B) present in CD64(hi)CD11b(hi) macrophages compared to BCG or BCG:(oex85B). After vaccination of mice with BCG:(Δ85B) or parental BCG and subsequent aerosol M. tuberculosis challenge, similar numbers of activated CD4(+) and CD8(+) T cells were detected in the lungs of infected mice for both groups, suggesting the reduced macrophage uptake observed by BCG:(Δ85B) did not alter host immunity. Further, vaccination with both BCG:(Δ85B) and parental BCG resulted in a comparable reduction in pulmonary M. tuberculosis load. These data reveal an unappreciated role for Ag85B in the interaction of mycobacteria with host cells and indicates that single protective antigens are dispensable for protective immunity induced by BCG. PMID:27060378

  1. Re: Sequential Combination of Mitomycin C Plus Bacillus Calmette-Guerin (BCG Is More Effective but More Toxic Than BCG Alone in Patients with Non–Muscle-Invasive Bladder Cancer in Intermediate-and High-Risk Patients: Final Outcome of CUETO 93009, A Randomized Prospective Trial

    Directory of Open Access Journals (Sweden)

    Eduardo Solsona

    2015-03-01

    Full Text Available EAU Guideline recommendation in non-muscle invasive bladder cancer (NMIBC is that patients who have intermediate or high risk for recurrence and intermediate risk for progression should receive early single dose intravesical chemotherapy followed by maintenance or a minimum of 1 year of BCG. Intravesical Mitomycin C (MMC plus Bacillus Calmette-Guerin (BCG treatment schemes were studied. However, MMC+BCG were not found to be superior to BCG alone (1,2. In the present study, authors conducted a randomized prospective trial on combination of MMC+BCG (n=192 or BCG alone (n=190. EORTC definition of NMIBC intermediate and high-risk patientswere included in the study. Unlike previous reported studies, disease-free interval at 5 years for MMC+BCG was found to be significantly better (HR: 0.57; 95% CI, 0.39 -0,83; p=0.003 than BCG alone. In an interim analysis, excessive toxicity was observed in MMC+BCG than BCG alone group. Consequently MMC dose was reduced from 30 mg to 10 mg. However, toxicity remained higher in the MMC+BCG group. Especially in EORTC highrisk NMIBCs, MMC+BCG is better than BCG alone, but with worse toxicity. In conclusion, despite some limitations, the results of Solsona et al. provided a new potential bladder-sparing management alternative, but it has higher toxicity. Additional studies are required to confirm these findings and availability of a less toxic intravesical chemotherapeutic agent.

  2. DIFFERENT CHARACTERISTICS OF INFECTION WITH MYCOBACTERIA IN GRANULOMA CELLS FROM MICE WITH LATENT TUBERCULOSIS INFECTION AND IN BONE MARROW AND PERITONEAL MACROPHAGES AFTER BCG VACCINE APPLICATION IN VITRO

    OpenAIRE

    E. G. Ufimtseva

    2014-01-01

    The aim of the study was to compare the content of BCG-mycobacteria in granulomas obtained from various organs of BALB/c mice with latent tuberculosis after in vivo exposure to BCG vaccine and in mouse bone marrow and peritoneal macrophages after BCG infection in vitro. The granuloma cells obtained from mice through 20 days, one and two months after their BCG-infecting in vivo were differed with respect to both the number of granulomas with macrophages containing the defined numbers of BCG-my...

  3. Evaluation of Immunogenicity and Protective Efficacy Elicited by Mycobacterium bovis BCG Overexpressing Ag85A Protein against Mycobacterium tuberculosis Aerosol Infection

    OpenAIRE

    Xu, Zheng Zhong; Chen, Xiang; Hu, Ting; MENG, CHUANG; Wang, Xiao Bo; Rao, Yan; Zhang, Xiao Ming; Yin, Yue Lan; Pan, Zhi Ming; Jiao, Xin An

    2016-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) is currently the only vaccine available for preventing tuberculosis (TB), however, BCG has varying success in preventing pulmonary TB. In this study, a recombinant BCG (rBCG::Ag85A) strain overexpressing the immunodominant Ag85A antigen was constructed, and its immunogenicity and protective efficacy were evaluated. Our results indicated that the Ag85A protein was successfully overexpressed in rBCG::Ag85A, and the Ag85A peptide–MHC complexes o...

  4. Dose of Incorporated Immunodominant Antigen in Recombinant BCG Impacts Modestly on Th1 Immune Response and Protective Efficiency against Mycobacterium tuberculosis in Mice

    Directory of Open Access Journals (Sweden)

    Hui Ma

    2014-01-01

    Full Text Available One approach for improving BCG efficacy is to utilize BCG as vehicle to develop recombinant BCG (rBCG strains overexpressing Mycobacterium tuberculosis (M. tb antigens. Also expression level of a candidate antigen should impact the final T cell responses conferred by rBCG. In this study, based on our previously constructed differential expression system, we developed two rBCG strains overexpressing M. tb chimeric antigen Ag856A2 (coding a recombinant ag85a with 2 copies of esat-6 inserted at Acc I site of ag85a at differential levels under the control of the subtly modified furA promoters. These two rBCG strains were used to vaccinate C57BL/6 mice and exploit dose of incorporated antigen in rBCG to optimize immune response and protective efficiency against M. tb challenge in mouse model. The results showed that rBCG strains overexpressing Ag856A2 at differential levels induced different antigen-specific IFN-γ production and comparable number of M. tb-specific CD4 T cells expressing IL-2. M. tb challenge experiment showed that rBCG strains afforded enhanced but comparable immune protection characterized by reduced bacillary load, lung pathology, and inflammation. These results suggested that the dose of antigens incorporated in rBCG can impact T cell immune responses but imposed no significantly differential protective efficacies.

  5. Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis.

    Science.gov (United States)

    Nandakumar, Subhadra; Kannanganat, Sunil; Dobos, Karen M; Lucas, Megan; Spencer, John S; Amara, Rama Rao; Plikaytis, Bonnie B; Posey, James E; Sable, Suraj B

    2016-01-01

    Heterologous prime-boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses in BCG-primed mice and investigated its BCG-booster potential. The Apa-specific T-cell response peaked 32-52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during the contraction-phase of BCG-response had a greater effect on the magnitude and functional quality of specific cellular and humoral responses compared to a boost at the peak of BCG-response. The cellular response increased following mucosal BCG-prime-Apa-subunit-boost strategy compared to Apa-subunit-prime-BCG-boost approach. However, parenteral BCG-prime-Apa-subunit-boost by a homologous route was the most effective strategy in-terms of enhancing specific T-cell responses during waning in the lung and spleen. Two Apa-boosters markedly improved waning BCG-immunity and significantly reduced Mycobacterium tuberculosis burdens post-challenge. Our results highlight the challenges of optimization of prime-boost regimens in mice where BCG drives persistent immune-activation and suggest that boosting with a heterologous vaccine may be ideal once the specific persisting effector responses are contracted. Our results have important implications for design of prime-boost regimens against tuberculosis in humans. PMID:27173443

  6. Molecular networks discriminating mouse bladder responses to intravesical bacillus Calmette-Guerin (BCG, LPS, and TNF-α

    Directory of Open Access Journals (Sweden)

    Dozmorov Igor

    2008-02-01

    Full Text Available Abstract Background Despite being a mainstay for treating superficial bladder carcinoma and a promising agent for interstitial cystitis, the precise mechanism of Bacillus Calmette-Guerin (BCG remains poorly understood. It is particularly unclear whether BCG is capable of altering gene expression in the bladder target organ beyond its well-recognized pro-inflammatory effects and how this relates to its therapeutic efficacy. The objective of this study was to determine differentially expressed genes in the mouse bladder following chronic intravesical BCG therapy and to compare the results to non-specific pro inflammatory stimuli (LPS and TNF-α. For this purpose, C57BL/6 female mice received four weekly instillations of BCG, LPS, or TNF-α. Seven days after the last instillation, the urothelium along with the submucosa was removed from detrusor muscle and the RNA was extracted from both layers for cDNA array experiments. Microarray results were normalized by a robust regression analysis and only genes with an expression above a conditional threshold of 0.001 (3SD above background were selected for analysis. Next, genes presenting a 3-fold ratio in regard to the control group were entered in Ingenuity Pathway Analysis (IPA for a comparative analysis in order to determine genes specifically regulated by BCG, TNF-α, and LPS. In addition, the transcriptome was precipitated with an antibody against RNA polymerase II and real-time polymerase chain reaction assay (Q-PCR was used to confirm some of the BCG-specific transcripts. Results Molecular networks of treatment-specific genes generated several hypotheses regarding the mode of action of BCG. BCG-specific genes involved small GTPases and BCG-specific networks overlapped with the following canonical signaling pathways: axonal guidance, B cell receptor, aryl hydrocarbon receptor, IL-6, PPAR, Wnt/β-catenin, and cAMP. In addition, a specific detrusor network expressed a high degree of overlap with the

  7. Multifocal sclerotic BCG spondylitis in a 13-year-old girl

    International Nuclear Information System (INIS)

    A case is reported of multifocal BCG osteomyelitis in a 13-year-old girl. The lesions in the skull, ribs and in several vertebrae were mainly sclerotic and healed with antituberculotic therapy. The case is unusual because of the late onset, sclerotic changes, and involvement of the spine. (orig.)

  8. BCG vaccine-induced neuroprotection in a mouse model of Parkinson's disease.

    Science.gov (United States)

    Yong, Jing; Lacan, Goran; Dang, Hoa; Hsieh, Terry; Middleton, Blake; Wasserfall, Clive; Tian, Jide; Melega, William P; Kaufman, Daniel L

    2011-01-01

    There is a growing interest in using vaccination with CNS antigens to induce autoreactive T cell responses that home to damaged areas in the CNS and ameliorate neurodegenerative disease. Neuroprotective vaccine studies have focused on administering oligodendrocyte antigens or Copaxone® in complete Freund's adjuvant (CFA). Theoretical considerations, however, suggest that vaccination with a neuronal antigen may induce more robust neuroprotective immune responses. We assessed the neuroprotective potential of vaccines containing tyrosine hydroxylase (a neuronal protein involved in dopamine synthesis) or Copaxone® in CFA in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Surprisingly, we observed that the main beneficial factor in these vaccines was the CFA. Since the major immunogenic component in CFA is Mycobacterium tuberculosis, which closely related to the bacille Calmette-Guérin (BCG) that is used in human vaccines, we tested BCG vaccination in the MPTP mouse model. We observed that BCG vaccination partially preserved markers of striatal dopamine system integrity and prevented an increase in activated microglia in the substantia nigra of MPTP-treated mice. These results support a new neuroprotective vaccine paradigm in which general (nonself-reactive) immune stimulation in the periphery can limit potentially deleterious microglial responses to a neuronal insult and exert a neurorestorative effect in the CNS. Accordingly, BCG vaccination may provide a new strategy to augment current treatments for a wide range of neuropathological conditions. PMID:21304945

  9. Draft Genome Sequence of the Vaccination Strain Mycobacterium bovis BCG S4-Jena.

    Science.gov (United States)

    Wibberg, Daniel; Winkler, Anika; Straube, Eberhard; Karrasch, Matthias; Keller, Peter M; Kalinowski, Jörn

    2016-01-01

    Here, we present the draft genome sequence of ITALIC! Mycobacterium bovisBCG S4-Jena, a tuberculosis vaccine strain. The genome of S4-Jena is represented by 48 scaffolds, consisting of 132 scaffolded contigs and amounting to a size of about 4.2 Mb. New genes potentially encoding a phage fragment were identified in the genome. PMID:27103721

  10. Hemopoietic stem cells preferential differentiation after transfer into lethally irradiated mice previously infected with BCG

    International Nuclear Information System (INIS)

    Following injection of bone marrow cells in lethally irradiated mice, previously infected with BCG regenerating hemopoietic cell populations differentiate along the leucocyte pathway to the detriment of erythroid lineage. Such a phenomenon persisting even if anemia of infected mice is increased by bleeding just before irradiation and reconstitution supports the hypothesis of preferential differentiation of stem cells

  11. The role of immunocompetent cells in the murine pulmonary granulomatous response induced by BCG

    International Nuclear Information System (INIS)

    The role of lymphocytes and macrophages in the BCG induced pulmonary granulomatous response in mice was studied. Pulmonary granulomas could be induced in mice by the intravenous injection of BCG suspended in light mineral oil. The granuloma formation with mononuclear cell infiltration reached a maximum after 3 weeks of injection (Chronic Granulomatous Response=CGR). An Accelerated Granulomatous Response (AGR) was elicited in sensitized mice (those undergoing the CGR) by an i.v. challenge with BCG suspended in saline and a maximum AGR developed within 4 days. The proliferative response of lymphocytes which were obtained from the lung was measured by 3H-Thymidine incorporation into DNA. In the case of CGR, the proliferative response stimulated by phytohemagglutinin (PHA) scarcely changed over 1 to 4 weeks of the response. In contrast, in the case of AGR, the proliferative responses stimulated by PHA rose to 10 times higher those of CGR at the point of maximum granuloma formation. These results suggested that the sensitized lymphocytes, challenged by the antigen, released some mediators related to mitogenic factors, chemotactic factors, and migration inhibitory factors, which might accelerate and enhancement of migration of T- and B-cells toward the granulomatous lesion. The pulmonary granulomatous response which was supressed by x-irradiation, was restored by intraperitoneal transplantation of syngeneic spleen cells, and thymus cells, but was only slightly affected by peritoneal exudate cells. Consequently it was suggested that lymphocytes played an important role in BCG-induced granuloma formation in mice. (auth.)

  12. VizieR Online Data Catalog: Morphology and structure of BCG (Zhao+, 2015)

    Science.gov (United States)

    Zhao, D.; Aragon-Salamanca, A.; Conselice, C. J.

    2015-09-01

    To study the structural properties of BCGs in galaxy groups and clusters, we use the BCG catalogue published by von den Linden (2007MNRAS.379..867V, Cat. J/MNRAS/379/867, hereafter L07). The 625 BCGs in L07 sample were visually classified by careful inspection of the SDSS images. (1 data file).

  13. Removal of BCG artifacts using a non-Kirchhoffian overcomplete representation.

    Science.gov (United States)

    Dyrholm, Mads; Goldman, Robin; Sajda, Paul; Brown, Truman R

    2009-02-01

    We present a nonlinear unmixing approach for extracting the ballistocardiogram (BCG) from EEG recorded in an MR scanner during simultaneous acquisition of functional MRI (fMRI). First, an overcomplete basis is identified in the EEG based on a custom multipath EEG electrode cap. Next, the overcomplete basis is used to infer non-Kirchhoffian latent variables that are not consistent with a conservative electric field. Neural activity is strictly Kirchhoffian while the BCG artifact is not, and the representation can hence be used to remove the artifacts from the data in a way that does not attenuate the neural signals needed for optimal single-trial classification performance. We compare our method to more standard methods for BCG removal, namely independent component analysis and optimal basis sets, by looking at single-trial classification performance for an auditory oddball experiment. We show that our overcomplete representation method for removing BCG artifacts results in better single-trial classification performance compared to the conventional approaches, indicating that the derived neural activity in this representation retains the complex information in the trial-to-trial variability. PMID:19342324

  14. Effect of revaccination with BCG in early childhood on mortality: randomised trial in Guinea-Bissau

    DEFF Research Database (Denmark)

    Roth, A.E.; Benn, Christine Stabell; Ravn, H.;

    2010-01-01

    children compared with controls was 2.69 (1.05 to 6.88) in the period after these campaigns. Throughout the trial, the effect of BCG revaccination on mortality was significantly different (P=0.006) in children who had received diphtheria-tetanus-pertussis (DTP) booster vaccination before enrolment (hazard...

  15. Targeted BCG Vaccination Against Severe Tuberculosis in Low-prevalence Settings Epidemiologic and Economic Assessment

    NARCIS (Netherlands)

    H. Korthals Altes; F. Dijkstra; A. Lugnèr; F. Cobelens; J. Wallinga

    2009-01-01

    Background: BCG vaccine protects against the severe forms of tuberculosis (TB) in children. Several low-prevalence countries are reviewing their policy, usually shifting from universal vaccination to vaccination of infants in high-risk groups only. We combined an epidemiologic analysis with a cost-e

  16. Construction, Expression and Identification of a Recombinant BCG Vaccine Encoding Human Mycobacterium Tuberculosis Heat Shock Protein 65

    Institute of Scientific and Technical Information of China (English)

    戴五星; 梁靓; 高红; 黄海浪; 陈智浩; 程继忠; 皇甫永穆

    2004-01-01

    Heat shock protein 65 (HSP65) is one of the most important protective immunogens against the tuberculosis infection. The signal sequence of antigen 85B and the whole HSP65 DNA sequence of human Mycobacterium tuberculosis (M. tuberculosis) were amplified from BCG genome and plasmid pCMV-MTHSP65 respectively by polymerase chain reactions (PCR). These two sequences were cloned into the plasmid pBCG-2100 under the control of the promoter of heat shock protein 70 (HSP70) from human M. tuberculosis, yielding the prokaryotic shuttle expression plasmid pBCG-SP-HSP65. Results of restriction endonuclease analysis, PCR detection and DNA sequencing analysis showed that the two cloned DNA sequences were consistent with those previously reported, and the direction of their inserting into the recombinant was correct and the reading frame had been maintained. The recombinants were electroporated into BCG to construct the recombinant BCG vaccine and induced by heating. The induced expression detected by SDS-PAGE showed that the content of 65 kD protein expressed in recombinant BCG was 35.69 % in total bacterial protein and 74.09 % in the cell lysate supernatants, suggesting that the recombinant HSP65 gene could express in BCG with high efficiency and the expressed proteins were mainly soluble. Western-blot showed that the secretive recombinant proteins could specifically combine with antibody against M.tuberculosis HSP65, indicating that the recombinant proteins possess the biological activity of HSP65.

  17. Neonatal BCG vaccination is associated with enhanced T-helper 1 immune responses to heterologous infant vaccines

    Directory of Open Access Journals (Sweden)

    Daniel H. Libraty

    2014-01-01

    Full Text Available Neonatal Bacille Calmette Guérin (BCG vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1 immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2–3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-γ (IFN-γ producing spot-forming cells (SFC to tetanus toxoid 2–3 months later. The frequency of IFN-γ producing SFC to polioviruses 1–3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA/Ionomycin was higher in 2–3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2–3 months later.

  18. Pattern and determinants of BCG immunisation delays in a sub-Saharan African community

    Directory of Open Access Journals (Sweden)

    Olusanya Bolajoko O

    2010-01-01

    Full Text Available Abstract Background Childhood immunisation is recognised worldwide as an essential component of health systems and an indispensable indicator of quality of care for vaccine-preventable diseases. While performance of immunisation programmes is more commonly measured by coverage, ensuring that every child is immunised at the earliest/appropriate age is an important public health goal. This study therefore set out to determine the pattern and predictors of Bacille de Calmette-Guérin (BCG immunisation delays in the first three months of life in a Sub-Saharan African community where BCG is scheduled at birth in order to facilitate necessary changes in current policy and practices for improved services. Methods A cross-sectional study in which immunisation delays among infants aged 0-3 months attending community-based BCG clinics in Lagos, Nigeria over a 2-year period from July 2005 to June 2007 were assessed by survival analysis and associated factors determined by multivariable logistic regression. Population attributable risk (PAR was computed for the predictors of delays. Results BCG was delayed beyond three months in 31.6% of all eligible infants. Of 5171 infants enrolled, 3380 (65.4% were immunised within two weeks and a further 1265 (24.5% by six weeks. A significantly higher proportion of infants born in hospitals were vaccinated in the first six weeks compared to those born outside hospitals. Undernourishment was predictive of delays beyond 2 and 6 weeks while treated hyperbilirubinaemia was associated with decreased odds for any delays. Lack of antenatal care and multiple gestations were also predictive of delays beyond 6 weeks. Undernourishment was associated with the highest PAR for delays beyond 2 weeks (18.7% and 6 weeks (20.8%. Conclusions BCG immunisation is associated with significant delays in this setting and infants at increased risk of delays can be identified and supported early possibly through improved maternal uptake of

  19. Re: Sequential Combination of Mitomycin C Plus Bacillus Calmette-Guerin (BCG) Is More Effective but More Toxic Than BCG Alone in Patients with Non–Muscle-Invasive Bladder Cancer in Intermediate-and High-Risk Patients: Final Outcome of CUETO 93009, A Randomized Prospective Trial

    OpenAIRE

    Eduardo Solsona; Rosario Madero; VenancioChantada

    2015-01-01

    EAU Guideline recommendation in non-muscle invasive bladder cancer (NMIBC) is that patients who have intermediate or high risk for recurrence and intermediate risk for progression should receive early single dose intravesical chemotherapy followed by maintenance or a minimum of 1 year of BCG. Intravesical Mitomycin C (MMC) plus Bacillus Calmette-Guerin (BCG) treatment schemes were studied. However, MMC+BCG were not found to be superior to BCG alone (1,2). In the present study, author...

  20. Protective effect of bacillus Calmette Guιrin (BCG vaccine in the prevention of leprosy: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Zodpey Sanjay

    2007-01-01

    Full Text Available Background: Although the role of bacillus Calmette Guιrin (BCG vaccine in the prevention of leprosy was hypothesized as early as 1939, its level of protective effect remained controversial. Aim: As a meta-analysis systematically combines the results from different studies, we summarize the protective effect of BCG vaccine in prevention of leprosy using meta-analytic procedures. Methods: Our search strategy included a computerized literature search, snowballing technique to identify potential studies, review of previously compiled lists of BCG studies and articles, contacting experts on BCG vaccination and manual search to locate articles in non-indexed journals. The present meta-analysis included 22 studies (6 trials, 2 cohort studies and 14 case-control studies on the role of BCG vaccine in the prevention of leprosy. The random effects model as described by DerSimonian and Laird was used to summarize the effect measures. For each summarization, a Chi-square test of heterogeneity was estimated. To strengthen the viewpoint further additional information from the studies which were not included in meta-analysis, was also utilized. Results: The summary protective effects calculated from trials, cohort studies and case-control studies were 43 (27-55, 62 (53-69 and 58 (47-67% respectively, which were statistically significant. These estimates confirmed the protective association between BCG vaccination and leprosy. Review of 29 studies focusing on the role of BCG vaccination in the prevention of leprosy revealed that not a single study reported a negative protective effect. Thirteen (44.8% studies demonstrated greater than or equal to 50% efficacy/effectiveness. Conclusion: There is sufficient and convincing evidence of the protective effect of BCG vaccine against leprosy, as reflected from the meta-analysis and overall review of 29 studies of BCG vaccination and leprosy.

  1. Immunogenic Properties of a BCG Adjuvanted Chitosan Nanoparticle-Based Dengue Vaccine in Human Dendritic Cells.

    Directory of Open Access Journals (Sweden)

    Taweewun Hunsawong

    2015-09-01

    Full Text Available Dengue viruses (DENVs are among the most rapidly and efficiently spreading arboviruses. WHO recently estimated that about half of the world's population is now at risk for DENV infection. There is no specific treatment or vaccine available to treat or prevent DENV infections. Here, we report the development of a novel dengue nanovaccine (DNV composed of UV-inactivated DENV-2 (UVI-DENV and Mycobacterium bovis Bacillus Calmette-Guerin cell wall components (BCG-CWCs loaded into chitosan nanoparticles (CS-NPs. CS-NPs were prepared by an emulsion polymerization method prior to loading of the BCG-CWCs and UVI-DENV components. Using a scanning electron microscope and a zetasizer, DNV was determined to be of spherical shape with a diameter of 372.0 ± 11.2 nm in average and cationic surface properties. The loading efficacies of BCG-CWCs and UVI-DENV into the CS-NPs and BCG-CS-NPs were up to 97.2 and 98.4%, respectively. THP-1 cellular uptake of UVI-DENV present in the DNV was higher than soluble UVI-DENV alone. DNV stimulation of immature dendritic cells (iDCs resulted in a significantly higher expression of DCs maturation markers (CD80, CD86 and HLA-DR and induction of various cytokine and chemokine productions than in UVI-DENV-treated iDCs, suggesting a potential use of BCG- CS-NPs as adjuvant and delivery system for dengue vaccines.

  2. In vitro T-cell profile induced by BCG Moreau in healthy Brazilian volunteers.

    Science.gov (United States)

    Ponte, C; Peres, L; Marinho, S; Lima, J; Siqueira, M; Pedro, T; De Luca, P; Cascabulho, C; Castello-Branco, L R; Antas, P R Z

    2015-01-01

    Tuberculosis (TB) remains the world's leading cause of morbidity and mortality. Although Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only vaccine currently in use, its efficacy is highly variable. It has been suggested that early antigenic presentation is a pivotal event leading to a better immune response in TB vaccine models. To investigate this further, we compared in vitro cell-mediated immune responses in the context of early sensitization with TB (i.e. healthy adults vaccinated with BCG when they were young, HD; n = 25) to those in its absence (i.e., newborns with naïve immunity to TB, UV; n = 10) by challenging mononuclear cells with BCG Moreau. After 48 hours, CD4+ and CD8+ T cells were harvested from both groups and stained for PD-1/CD25/ FOXP3. In addition, supernatants were assayed for a broad range of cytokines using an array system. The HD group showed robust reactivity to Protein Purified Derivative and BCG while the naïve, UV group did not. Similarly, in terms of PD-1 expression and Treg cells (CD4+/CD25high(+)/FOXP3+), only the HD group showed higher levels in CD4 lymphocytes. Otherwise, only the UV group showed expression of CD25dim+ as an activation marker dependent on BCG infection. In terms of cytokines, the HD group showed higher levels of Th1 (IL-2/TNF-α/IFN-γ) and regulatory (IL-10) profiles, with monocytes, but not Tr1 cells, acting as the main source of IL-10. Taken together, our results highlight critical roles of early sensitization with TB in mounting cell-mediated immune responses. PMID:25483636

  3. The second Geneva Consensus: Recommendations for novel live TB vaccines.

    Science.gov (United States)

    Walker, K B; Brennan, M J; Ho, M M; Eskola, J; Thiry, G; Sadoff, J; Dobbelaer, R; Grode, L; Liu, M A; Fruth, U; Lambert, P H

    2010-03-01

    Infection with Mycobacterium tuberculosis continues to be a major public health burden in most developing parts of the world and efforts to develop effective strategies for containing the disease remain a priority. It has long been evident that effective mass vaccination programmes are a cost effective and efficient approach to controlling communicable diseases in a public health setting and tuberculosis (TB) continues to be a major target. One approach with increasing acceptance is based upon on live mycobacterial vaccines, either as recombinant BCG or rationally attenuated M. tuberculosis, thus generating a new live TB vaccine. The Geneva Consensus published in March 2005 set out the opinion on priorities and requirements for developing live mycobacterial vaccines for Phase I trials. In the intervening period much progress has been made in both preclinical and clinical development of new TB vaccines and has provided the impetus for organising the second Geneva Consensus (held at WHO headquarters, April 2009) to discuss issues, including: i. Explore the regulatory requirements for live TB vaccines to enter Phase I trials, in particular those based on attenuated M. tuberculosis. Particular attention was paid to the characterisation and safety package likely to be required, including issues of attenuation, the presence of antibiotic resistance markers in live vaccines and the nature of any attenuated vaccine phenotype. ii. To identify the general criteria for further clinical development from Phase I through to Phase III. iii. Obtain a perspective of the regulatory landscape of developing countries where Phase II and III trials are to be held. iv. Review manufacturing considerations for live TB vaccines and relevance of the WHO and European Pharmacopeia guidelines and requirements for BCG vaccine. v. Consider requirements and associated issues related to the use of these new vaccines within an existing BCG vaccination programme. PMID:20074686

  4. Pharmaceutical characterization of Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine used for the treatment of superficial bladder cancer.

    Science.gov (United States)

    Groves, M J

    1993-06-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine, developed in the 1920s as a treatment and prophylactic for tuberculosis, has proved to be a nonspecific stimulant of the immune system and is now the major form of clinical immunotherapy approved for the treatment of superficial bladder cancer in the United States. However, methods for the production and physical characterization of the vaccine have not been significantly developed since Calmette and Guérin first devised their process for attenuating the organism in 1908. When reconstituted with sterile water immediately before use, the vaccine consists of a suspension of cellular fragments and aggregates and a mixture of dead and living cells. The dose is determined by the number of colony-forming units that develop when the vaccine is allowed to grow in a nutrient medium. This measurement of dose and viability is misleading because each cellular aggregate may consist of several hundred individual cells, but only one need be living to give rise to a single visible colony. Viability should therefore be measured on the basis of residual ATP levels. In this report, the mode of action of BCG vaccine against bladder cancer is reviewed, and attention is drawn to some factors that may need to be controlled during manufacturing and subsequent quality assurance procedures. The morphology of the various parts of the complex pleomorphic life cycle of this Mycobacterium species has been investigated, and the vaccine has been physically evaluated to provide a characterization by contemporary methodologies, including measurement of ATP content and particle size distribution of the dispersed mycobacterial aggregates. PMID:8331524

  5. Vaccination of Cattle with a CpG Oligodeoxynucleotide-Formulated Mycobacterial Protein Vaccine and Mycobacterium bovis BCG Induces Levels of Protection against Bovine Tuberculosis Superior to Those Induced by Vaccination with BCG Alone

    OpenAIRE

    Wedlock, D. Neil; Denis, Michel; Skinner, Margot A.; Koach, Jessica; de Lisle, Geoffrey W.; Vordermeier, H. Martin; Hewinson, R Glyn; van Drunen Littel-van den Hurk, Sylvia; Babiuk, Lorne A.; Hecker, Rolf; Buddle, Bryce M.

    2005-01-01

    The development of a subunit protein vaccine for bovine tuberculosis which could be used either in combination with Mycobacterium bovis BCG (to improve the efficacy of that vaccine) or alone would offer significant advantages over currently available strategies. A study was conducted with cattle to determine the protective efficacy of a strategy based on concurrent immunization with an M. bovis culture filtrate (CFP) vaccine and BCG compared to vaccination with either vaccine alone. One group...

  6. Drug: D03063 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03063 Drug BCG ... vaccine (USP); Tice BCG ... (TN) Immunizing agent [active] ATC code: L03AX03 Anatomi ... UNOSTIMULANTS L03AX Other immunostimulants L03AX03 BCG ... vaccine D03063 BCG ... vaccine (USP) PubChem: 17397218 ...

  7. Enhanced and durable protective immune responses induced by a cocktail of recombinant BCG strains expressing antigens of multistage of Mycobacterium tuberculosis.

    Science.gov (United States)

    Liang, Jinping; Teng, Xindong; Yuan, Xuefeng; Zhang, Ying; Shi, Chunwei; Yue, Tingting; Zhou, Lei; Li, Jianrong; Fan, Xionglin

    2015-08-01

    Although Bacillus Calmette-Guérin (BCG) vaccine confers protection from Mycobacterium tuberculosis infection in children, its immune protection gradually wanes over time, and consequently leads to an inability to prevent the reactivation of latent infection of M. tuberculosis. Therefore, improving BCG for better control of tuberculosis (TB) is urgently needed. We thus hypothesized that recombinant BCG overexpressing immunodominant antigens expressed at different growth stages of M. tuberculosis could provide a more comprehensive protection against primary and latent M. tuberculosis infection. Here, a novel cocktail of recombinant BCG (rBCG) strains, namely ABX, was produced by combining rBCG::85A, rBCG::85B, and rBCG::X, which overexpressed respective multistage antigens Ag85A, Ag85B, and HspX of M. tuberculosis. Our results showed that ABX was able to induce a stronger immune protection than individual rBCGs or BCG against primary TB infection in C57BL/6 mice. Mechanistically, the immune protection was attributed to stronger antigen-specific CD4(+) Th1 responses, higher numbers of IFN-γ(+) CD4(+) TEM and IL-2(+) CD8(+) TCM cells elicited by ABX. These findings thus provide a novel strategy for the improvement of BCG efficacy and potentially a promising prophylactic TB vaccine candidate, warranting further investigation. PMID:25974877

  8. Theoretical and methodological aspects of BCG vaccine from the discovery of Calmette and Guérin to molecular biology. A review.

    Science.gov (United States)

    Lugosi, L

    1992-10-01

    The BCG vaccine has been used to prevent tuberculosis since 1921 and applied for immunostimulation in neoplasia since the 1960s. Both the preventive and immunostimulation effects have been evaluated and communicated with contradictory, positive and negative conclusions. For an objective evaluation and interpretation of the protective efficacy, effectiveness and efficiency of the BCG vaccination it must be considered that: (1) several BCG substrains have been developed in manufacturing laboratories that differ in the residual virulence which determines immunogenicity and reactogenicity; (2) various liquid and freeze-dried BCG vaccine production methods are used, resulting in different BCG viable units per dose; (3) quantitative bioassay methods are not yet being used for statistical quality control of the vaccine; (4) BCG products are applied in various demographical, epidemiological and socioeconomic conditions with different vaccination policies; (5) inadequate biostatistical models are often used to analyse efficacy, effectiveness and adverse reactions. The same conditions influence the precise evaluation of BCG immunostimulation in neoplasia. Recombinant DNA technology will modify production methods, and explain at the molecular level the mechanism of the protective effects BCG confers in tuberculosis and immunostimulation in neoplasia. High level laboratory techniques and biostatistical methods, based on probability logic and inductive inference, ensure appropriate experimental designs and the exact analysis of laboratory data and the results of vaccination policies. They will lead to the evaluation of the protective effect of BCG in order to reduce the BCG contradictions. PMID:1493232

  9. Monosodium Urate Crystals Promote Innate Anti-Mycobacterial Immunity and Improve BCG Efficacy as a Vaccine against Tuberculosis.

    Science.gov (United States)

    Taus, Francesco; Santucci, Marilina B; Greco, Emanuela; Morandi, Matteo; Palucci, Ivana; Mariotti, Sabrina; Poerio, Noemi; Nisini, Roberto; Delogu, Giovanni; Fraziano, Maurizio

    2015-01-01

    A safer and more effective anti-Tuberculosis vaccine is still an urgent need. We probed the effects of monosodium urate crystals (MSU) on innate immunity to improve the Bacille Calmette-Guerin (BCG) vaccination. Results showed that in vitro MSU cause an enduring macrophage stimulation of the anti-mycobacterial response, measured as intracellular killing, ROS production and phagolysosome maturation. The contribution of MSU to anti-mycobacterial activity was also shown in vivo. Mice vaccinated in the presence of MSU showed a lower number of BCG in lymph nodes draining the vaccine inoculation site, in comparison to mice vaccinated without MSU. Lastly, we showed that MSU improved the efficacy of BCG vaccination in mice infected with Mycobacterium tuberculosis (MTB), measured in terms of lung and spleen MTB burden. These results demonstrate that the use of MSU as adjuvant may represent a novel strategy to enhance the efficacy of BCG vaccination. PMID:26023779

  10. Activity in mice of recombinant BCG-EgG1Y162 vaccine for Echinococcus granulosus infection.

    Science.gov (United States)

    Ma, Xiumin; Zhao, Hui; Zhang, Fengbo; Zhu, Yuejie; Peng, Shanshan; Ma, Haimei; Cao, Chunbao; Xin, Yan; Yimiti, Delixiati; Wen, Hao; Ding, Jianbing

    2016-01-01

    Cystic hydatid disease is a zoonotic parasitic disease caused by Echinococcus granulosus which is distributed worldwide. The disease is difficult to treat with surgery removal is the only cure treatment. In the high endemic areas, vaccination of humans is believed a way to protect communities from the disease. In this study we vaccinated BALB/c mice with rBCG-EgG1Y162, and then detected the level of IgG and IgE specifically against the recombinant protein by ELISA, rBCG-EgG1Y162 induced strong and specific cellular and humoral immune responses. In vitro study showed that rBCG-EgG1Y162 vaccine not only promote splenocytes proliferation but also active T cell. In addition, the rBCG-EgG1Y162 induced a protection in the mice against secondary infection of Echinococcus granulosus. PMID:26266551

  11. Effect of BCG cell-wall skeleton immunotherapy on the peripheral blood lymphocytes in patients with lung cancer after radiotherapy

    International Nuclear Information System (INIS)

    The effect of radiotherapy on peripheral blood lymphocytes (PBL) of lung cancer and the effect of BCG cell-wall skeleton (BCG-CWS) on recovery of impaired PBL were examined. A remarkable depression of the absolute number of E- or EAC-rosette cells and of the response of PBL to mitogens were observed immediately after radiotherapy, and these continued for several months. With BCG-CWS immunotherapy, the response of PBL to phytohemagglutinin recovered rapidly, compared with non-vaccinated patients. The response of PBL to pokeweed mitogen seemed to give similar results. These results suggested that BCG-CWS injection to the patient receiving radiotherapy was effective for recovery of T-cell response. (author)

  12. [Association between severe tuberculosis in children and previous BCG immunization in a national referral hospital, Peru 1990-2000].

    Science.gov (United States)

    Llanos-Tejada, Félix; del Castillo, Hernán

    2012-03-01

    The objective of the study was to determine the association between BCG immunization and severe tuberculosis (TB). We performed a retrospective study, including medical records from patients of the pneumology department at the National Children's Institute in Peru, between the years 1990-2000. A total of 2106 TB cases were reviewed, from them 259 patients were severe (miliary TB or meningoencephalitic TB). From all, 497 cases did not have history of BCG vaccination, 202 had severe TB and 295 non-severe TB (OR = 0.05, 95% CI = 0.03 to 0.07). In conclusion, children diagnosed with TB and who have been immunized with BCG, has 94% lower risk of developing severe TB, compared to children with TB non-immunized with BCG. PMID:22510912

  13. Repeated BCG treatment of mouse bladder selectively stimulates small GTPases and HLA antigens and inhibits single-spanning uroplakins

    Directory of Open Access Journals (Sweden)

    O'Donnell Michael A

    2007-11-01

    Full Text Available Abstract Background Despite being a mainstay for treating superficial bladder carcinoma and a promising agent for interstitial cystitis, the precise mechanism of Bacillus Calmette-Guerin (BCG remains poorly understood. It is particularly unclear whether BCG is capable of altering gene expression beyond its well-recognized pro-inflammatory effects and how this relates to its therapeutic efficacy. The objective of this study was to determine differentially expressed genes in the mouse bladder following repeated intravesical BCG therapy. Methods Mice were transurethrally instilled with BCG or pyrogen-free on days 1, 7, 14, and 21. Seven days after the last instillation, urothelia along with the submucosa was removed and amplified ds-DNA was prepared from control- and BCG-treated bladder mucosa and used to generate suppression subtractive hybridization (SSH. Plasmids from control- and BCG-specific differentially expressed clones and confirmed by Virtual Northern were then purified and the inserts were sequenced and annotated. Finally, chromatin immune precipitation combined with real-time polymerase chain reaction assay (ChIP/Q-PCR was used to validate SSH-selected transcripts. Results Repeated intravesical BCG treatment induced an up regulation of genes associated with antigen presentation (B2M, HLA-A, HLA-DQA1, HLA-DQB2, HLA-E, HLA-G, IGHG, and IGH and representatives of two IFNγ-induced small GTPase families: the GBPs (GBP1, GBP2, and GBP5 and the p47GTPases (IIGTP1, IIGTP2, and TGTP. Genes expressed in saline-treated bladders but down-regulated by BCG included: the single-spanning uroplakins (UPK3a and UPK2, SPRR2G, GSTM5, and RSP 19. Conclusion Here we introduced a hypothesis-generator approach to determine key genes involved in the urothelium/sumbmucosa responses to BCG therapy. Urinary bladder responds to repeated BCG treatment by up-regulating not only antigen presentation-related genes, but also GBP and p47 small GTPases, both potentially

  14. Repeated BCG treatment of mouse bladder selectively stimulates small GTPases and HLA antigens and inhibits single-spanning uroplakins

    International Nuclear Information System (INIS)

    Despite being a mainstay for treating superficial bladder carcinoma and a promising agent for interstitial cystitis, the precise mechanism of Bacillus Calmette-Guerin (BCG) remains poorly understood. It is particularly unclear whether BCG is capable of altering gene expression beyond its well-recognized pro-inflammatory effects and how this relates to its therapeutic efficacy. The objective of this study was to determine differentially expressed genes in the mouse bladder following repeated intravesical BCG therapy. Mice were transurethrally instilled with BCG or pyrogen-free on days 1, 7, 14, and 21. Seven days after the last instillation, urothelia along with the submucosa was removed and amplified ds-DNA was prepared from control- and BCG-treated bladder mucosa and used to generate suppression subtractive hybridization (SSH). Plasmids from control- and BCG-specific differentially expressed clones and confirmed by Virtual Northern were then purified and the inserts were sequenced and annotated. Finally, chromatin immune precipitation combined with real-time polymerase chain reaction assay (ChIP/Q-PCR) was used to validate SSH-selected transcripts. Repeated intravesical BCG treatment induced an up regulation of genes associated with antigen presentation (B2M, HLA-A, HLA-DQA1, HLA-DQB2, HLA-E, HLA-G, IGHG, and IGH) and representatives of two IFNγ-induced small GTPase families: the GBPs (GBP1, GBP2, and GBP5) and the p47GTPases (IIGTP1, IIGTP2, and TGTP). Genes expressed in saline-treated bladders but down-regulated by BCG included: the single-spanning uroplakins (UPK3a and UPK2), SPRR2G, GSTM5, and RSP 19. Here we introduced a hypothesis-generator approach to determine key genes involved in the urothelium/sumbmucosa responses to BCG therapy. Urinary bladder responds to repeated BCG treatment by up-regulating not only antigen presentation-related genes, but also GBP and p47 small GTPases, both potentially serving to mount a resistance to the replication of the

  15. The effects of BCG, cyclophosphamide and x-radiation on reticuloendothelial system and immune responsiveness in mice, 1

    International Nuclear Information System (INIS)

    The effects of BCG and x-radiation of sublethal dose on reticuloendothelial system (RES) were studied in mice. An attempt was also made to evaluate the action of BCG on the recovery of immune responsiveness in irradiated mice. Carbon clearance test and measurement of spread macrophage in peritoneal cells were used to assay the function of RES. The result of carbon clearance was in good accordance with the one of macrophage spreading test. Either intracutaneous or intravenous administration of BCG increased the activity of RES, and 3 to 5 weeks later, the functional levels of RES reached a maximum. When BCG was given intravenously, the highly increased level of phagocytic activity was obtained even one week after BCG injection. Whereas x-radiation of sublethal dose caused a marked reduction of the number of peritoneal cells, the decrease of RES activity was not found. Although x-radiation suppressed markedly the immune response to sheep red blood cells (SRBC), delayed type reactivity recovered quickly to a normal level. The production of plaque forming cells (PEC) in spleen also recovered within 2 weeks after x-radiation and thereafter increased rather, while PFC in the draining lymph node reduced markedly and its recovery was protracted. BCG inoculation in x-radiated mice could not increase the number of peritoneal cells while it increased the activity of RES and the immune responsiveness to SRBC. BCG inoculation made mice extremely susceptible to pseudomonas infection either 2 to 3 weeks after i.v. inoculation or 5 weeks after i.c. inoculation. But a marked resistance than normal controls was found 10 weeks after the i.c. inoculation of BCG. On the other hand, x-radiation caused a serious damage to protective activity against pseudomonas infection and no increase of resistance throughout experimental period. (auth.)

  16. Intranasal Boosting with an Adenovirus-Vectored Vaccine Markedly Enhances Protection by Parenteral Mycobacterium bovis BCG Immunization against Pulmonary Tuberculosis

    OpenAIRE

    Santosuosso, Michael; McCormick, Sarah; Zhang, Xizhong; Zganiacz, Anna; Xing, Zhou

    2006-01-01

    Parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. We examined a heterologous prime-boost regimen utilizing BCG as a prime vaccine and our recently described adenoviral vector expressing Ag85A (AdAg85A) as a boost vaccine. Since we recently demonstrated that a single intranasal but not intramuscular immunization with AdAg85A was able to...

  17. Lactoferrin enhanced efficacy of the BCG vaccine to generate host protective responses against challenge with virulent Mycobacterium tuberculosis

    OpenAIRE

    Hwang, Shen-An; Wilk, Katarzyna M.; Budnicka, Monika; Olsen, Margaret; Bangale, Yogesh A.; Hunter, Robert L.; Kruzel, Marian L.; Actor, Jeffrey K.

    2007-01-01

    Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a disease with world wide consequences, affecting nearly a third of the world’s population. The established vaccine for TB, an attenuated strain of Mycobacterium bovis Calmette Guerin (BCG), has existed since 1921. Lactoferrin, an iron binding protein found in mucosal secretions and granules of neutrophils was hypothesized to be an ideal adjuvant to enhance the efficacy of the BCG vaccine, specifically because of previous repor...

  18. The effect of BCG on iron metabolism in the early neonatal period: A controlled trial in Gambian neonates

    OpenAIRE

    Prentice, S; Jallow, MW; Prentice, AM; MRC-International Nutrition Group

    2015-01-01

    : Bacillus Calmette-Guerin (BCG) vaccination has been reported to protect neonates from non-tuberculous pathogens, but no biological mechanism to explain such effects is known. We hypothesised that BCG produces broad-spectrum anti-microbial protection via a hepcidin-mediated hypoferraemia, limiting iron availability for pathogens. To test this we conducted a trial in 120 Gambian neonates comparing iron status in the first 5-days of life after allocation to: (1) All routine vaccinations at bir...

  19. Influence of whole body irradiation on BCG contact suppression of a rat sarcoma and tumour-specific immunity

    International Nuclear Information System (INIS)

    Experiments described here were carried out to assess the influence of host immunosuppression on Bacillus Calmette Guerin (BCG) contact suppression of a syngenetically transplanted 3-methylcholanthrene-induced rat sarcoma, Mc7, by 450 rad whole body γ radiation at 7 rad/min. The results suggest that augmented systemic responses to tumour-associated rejection antigens are not essential for BCG contact suppression but it is stated that the nature of the responses involved have yet to be elucidated. (U.K.)

  20. Is there a correlation between the size of the BCG scar and renal scar of urinary tract infections in children?

    OpenAIRE

    Salih Kavukçu; Demet Alaygut; Belde Kasap; Alper Soylu; Gamze Çapakaya; Mehmet Türkmen

    2013-01-01

    Objective: Pyelonephritis cause cellular death, and developmentof scars in kidneys. The aim of this study is todemonstrate a correlation (if any) between renal scar, andsize of the scar induced by BCG vaccine in children whohad experienced urinary tract infections. In case of detectionof any correlation, BCG scar formation can be usedas a determinative marker of renal scars, which developfollowing urinary tract infection.Methods: Patients with a history of urinary tract infectionat least 4 mo...

  1. Quality control of BCG vaccine by WHO: a review of factors that may influence vaccine effectiveness and safety.

    OpenAIRE

    Milstien, J. B.; J. J. Gibson

    1990-01-01

    WHO oversees the quality control of BCG vaccine via a system that includes regular testing of products by in vitro methods and clinical trials. Three parent strains of BCG (Glaxo-1077, Tokyo-172, and Pasteur-1173P2) account for over 90% of the vaccines currently in use worldwide. Important characteristics of the vaccine preparations are summarized here, along with their physical-chemical properties. In instances where diagnostic criteria for tuberculosis are stringent, there is no evidence th...

  2. Assessment of safety and interferon gamma responses of Mycobacterium bovis BCG vaccine in goat kids and milking goats.

    Science.gov (United States)

    Pérez de Val, Bernat; Vidal, Enric; López-Soria, Sergio; Marco, Alberto; Cervera, Zoraida; Martín, Maite; Mercader, Irene; Singh, Mahavir; Raeber, Alex; Domingo, Mariano

    2016-02-10

    Vaccination of domestic animals has emerged as an alternative long-term strategy for the control of tuberculosis (TB). A trial under field conditions was conducted in a TB-free goat herd to assess the safety of the Mycobacterium bovis BCG vaccine. Eleven kids and 10 milking goats were vaccinated with BCG. Bacterial shedding and interferon gamma (IFN-γ) responses were monitored throughout the study. Comprehensive pathological examination and mycobacterial culture of target tissues were performed. BCG vaccine strain was only isolated from the draining lymph node of the injection site of a kid euthanized at week 8 post-vaccination. The remaining animals were euthanized at week 24. Six out of 20 showed small granulomas at the injection site. BCG shedding was not detected in either faeces or in milk throughout the study. All vaccinated kids showed BCG-induced IFN-γ responses at week 8 post-vaccination. BCG vaccination of goats showed no lack of biological safety for the animals, environment and public health, and local adverse reactions were negligible. PMID:26795364

  3. Recombinant BCG prime and PPE protein boost provides potent protection against acute Mycobacterium tuberculosis infection in mice.

    Science.gov (United States)

    Yang, Enzhuo; Gu, Jin; Wang, Feifei; Wang, Honghai; Shen, Hongbo; Chen, Zheng W

    2016-04-01

    Since BCG, the only vaccine widely used against tuberculosis (TB) in the world, provides varied protective efficacy and may not be effective for inducing long-term cellular immunity, it is in an urgent need to develop more effective vaccines and more potent immune strategies against TB. Prime-boost is proven to be a good strategy by inducing long-term protection. In this study, we tested the protective effect against Mycobacterium tuberculosis (Mtb) challenge of prime-boost strategy by recombinant BCG (rBCG) expressing PPE protein Rv3425 fused with Ag85B and Rv3425. Results showed that the prime-boost strategy could significantly increase the protective efficiency against Mtb infection, characterized by reduction of bacterial load in lung and spleen, attenuation of tuberculosis lesions in lung tissues. Importantly, we found that Rv3425 boost, superior to Ag85B boost, provided better protection against Mtb infection. Further research proved that rBCG prime-Rv3425 boost could obviously increase the expansion of lymphocytes, significantly induce IL-2 production by lymphocytes upon PPD stimulation, and inhibit IL-6 production at an early stage. It implied that rBCG prime-Rv3425 boost opted to induce Th1 immune response and provided a long-term protection against TB. These results implicated that rBCG prime-Rv3425 boost is a potent and promising strategy to prevent acute Mtb infection. PMID:26792673

  4. Lack of a Negative Effect of BCG-Vaccination on Child Psychomotor Development

    DEFF Research Database (Denmark)

    Kjærgaard, Jesper; Stensballe, Lone Graff; Birk, Nina Marie;

    2016-01-01

    OBJECTIVES: To assess the non-specific effect of Bacillus Calmette-Guérin (BCG) vaccination at birth on psychomotor development. DESIGN: This is a pre-specified secondary outcome from a randomised, clinical trial. SETTING: Maternity units and paediatric wards at three university hospitals in...... MEASURES: Psychomotor development measured using Ages and Stages Questionnaire (ASQ) completed by the parents at 12 months. Additionally, parents of premature children (gestational age < 37 weeks) completed an ASQ at 6 and 22 months. Developmental assessment was available for 3453/4262 (81%). RESULTS: The...... -7.8 points (-20.6 to 5.0, p = 0.23), d = -0.23 (-0.62 to 0.15). CONCLUSIONS: A negative non-specific effect of BCG vaccination at birth on psychomotor development was excluded in term children. TRIAL REGISTRATION: ClinicalTrials.gov NCT01694108....

  5. Analysis of Service Quality Management in the Materials Industry using the BCG Matrix Method

    OpenAIRE

    Adrian Ioana; Vasile Mirea; Cezar Balescu

    2009-01-01

    For each product or service, the area of the circle represents the value of its sales. The BCG (Boston Consulting Group) matrix thus offers a very useful map of the organization's service strengths and weaknesses, at least in terms of current profitability, as well as the likely cash flows. The criteria function concept consists of transforming the criteria function (CF) in a qualityeconomical matrix MQE. The levels of prescribing the criteria function were obtained by using a composition alg...

  6. BOSTON CONSULTING GROUP (BCG) MATRIX ANALYSIS DURING THE STRATEGIC PLANNING OF GOVERNMENT ADMINISTRATION INFORMATION SYSTEMS (GAIS)

    OpenAIRE

    Maček, Vlatko; Brumec, Josip; Dušak, Vesna

    2000-01-01

    This paper deals with the BCG matrix analysis applied during the Strategic Planning of a selected group of Government Administration Information Systems (GAIS) i. e. Customs Administration Information System (CAIS), Tax Administration Information System (TAIS), Treasury Information System (TRIS) and Local Government Information System (LGIS). This selection is taken to be a representative corpus of the GAIS. The characteristics of the GA members will also be mentioned. These include its impor...

  7. Stimulation of alveolar macrophages by BCG vaccine enhances the process of lung fibrosis induced by bleomycin.

    Science.gov (United States)

    Chyczewska, E; Chyczewski, L; Bańkowski, E; Sułkowski, S; Nikliński, J

    1993-01-01

    It was found that the BCG vaccine injected subcutaneously to the rats enhances the process of lung fibrosis induced by bleomycin. Pretreatment of rats with this vaccine results in accumulation of activated macrophages in lung interstitium and in the bronchoalveolar spaces. It may be suggested that the activated macrophages release various cytokines which may stimulate the proliferation of fibroblasts and biosynthesis of extracellular matrix components. PMID:7505240

  8. Ultrastructural characteristics of type A epithelioid cells during BCG-granulomatosis and treatment with lysosomotropic isoniazid.

    Science.gov (United States)

    Shkurupii, V A; Kozyaev, M A; Nadeev, A P

    2006-04-01

    We studied BCG-granulomas, their cellular composition, and ultrastructure of type A epithelioid cells in the liver of male BALB/c mice with spontaneous granulomatous inflammation. The animals received free isoniazid or isoniazid conjugated with lysosomotropic intracellularly prolonged matrix (dialdehyde dextran, molecular weight 65-75 kDa). Lysosomotropic isoniazid was accumulated in the vacuolar apparatus of epithelioid cells and produced a stimulatory effect on plastic processes in these cells. PMID:17152378

  9. Subclinical miliary Mycobacterium bovis following BCG immunotherapy for transitional cell carcinoma of the bladder

    OpenAIRE

    Choi, Chang-ho Ryan; Lee, Sang Oh; Smith, Geoff

    2014-01-01

    The authors present an unusual case of a 51-year-old man who developed relatively mild non-specific symptoms following intravesical BCG instillation for superficial transitional cell carcinoma of the bladder, with radiological investigations demonstrating typical features of miliary tuberculosis (TB). Transbronchial biopsy showed small foci of poorly formed granuloma suggestive of Mycobacterium infection. The patient's respiratory symptoms only became apparent 7 days after discharge having ha...

  10. Extensive Mycobacterium bovis BCG Infection of Liver Parenchymal Cells in Immunocompromised Mice

    OpenAIRE

    Mills, John W.; Ryan, Lynn; LaCourse, Ronald; North, Robert J.

    2001-01-01

    A histologic study was performed on the livers of wild-type (WT), severe combined immunodeficient (SCID), hydrocortisone acetate (HC)-treated WT, and HC-treated SCID mice infected intravenously with 105 CFU of Mycobacterium bovis BCG. It was found that infection progressed faster in SCID mice than in WT mice and that HC treatment caused exacerbation of infection in both types of mice. In all cases infection in the liver was confined to granulomas that were populated predominantly by macrophag...

  11. 腹膜播種に対するBCG. Levamisole免疫療法

    OpenAIRE

    小林, 征二

    1983-01-01

    BCG and levamisole (LMS) immunotherapies were applied to an experimental model of cancer in the digestive organs by considering the abdominal wall as the intestinal tract wall. Ehrlich ascites tumor cells transplanted subcutaneously into the abdominal wall of mice invaded to the parietal peritoneum in approximately two weeks. Afterwards the tumor cells appeared in the peritoneal cavity, following retention of ascites. Almost all tumor bearing mice died within three weeks after the appearance ...

  12. Attenuated Host Resistance against Mycobacterium bovis BCG Infection in Mice Lacking Osteopontin

    OpenAIRE

    Nau, Gerard J.; Liaw, Lucy; Chupp, Geoffrey L.; Berman, Jeffrey S.; Hogan, Brigid L.M.; Young, Richard A.

    1999-01-01

    Expression of the cytokine osteopontin (OPN) is elevated in granulomas caused by Mycobacterium tuberculosis. We tested the hypothesis that OPN contributes to host protection in a mouse model of mycobacterial infection. When infected with Mycobacterium bovis BCG, mice lacking a functional OPN gene had more severe infections characterized by heavier bacterial loads and a delayed clearance of the bacteria. The OPN-null mice had greater granuloma burdens consistent with the elevated bacterial loa...

  13. Application of RAD-BCG calculator to Hanford's 300 area shoreline characterization dataset

    Energy Technology Data Exchange (ETDEWEB)

    Antonio, Ernest J.; Poston, Ted M.; Tiller, Brett L.; Patton, Gene W.

    2003-07-01

    Abstract. In 2001, a multi-agency study was conducted to characterize potential environmental effects from radiological and chemical contaminants on the near-shore environment of the Columbia River at the 300 Area of the U.S. Department of Energy’s Hanford Site. Historically, the 300 Area was the location of nuclear fuel fabrication and was the main location for research and development activities from the 1940s until the late 1980s. During past waste handling practices uranium, copper, and other heavy metals were routed to liquid waste streams and ponds near the Columbia River shoreline. The Washington State Department of Health and the Pacific Northwest National Laboratory’s Surface Environmental Surveillance Project sampled various environmental components including river water, riverbank spring water, sediment, fishes, crustaceans, bivalve mollusks, aquatic insects, riparian vegetation, small mammals, and terrestrial invertebrates for analyses of radiological and chemical constituents. The radiological analysis results for water and sediment were used as initial input into the RAD-BCG Calculator. The RAD-BCG Calculator, a computer program that uses an Excel® spreadsheet and Visual Basic® software, showed that maximum radionuclide concentrations measured in water and sediment were lower than the initial screening criteria for concentrations to produce dose rates at existing or proposed limits. Radionuclide concentrations measured in biota samples were used to calculate site-specific bioaccumulation coefficients (Biv) to test the utility of the RAD-BCG-Calculator’s site-specific screening phase. To further evaluate site-specific effects, the default Relative Biological Effect (RBE) for internal alpha particle emissions was reduced by half and the program’s kinetic/allometric calculation approach was initiated. The subsequent calculations showed the initial RAD-BCG Calculator results to be conservative, which is appropriate for screening purposes.

  14. Effects of diet and genetics on Mycobacterium bovis BCG vaccine efficacy in inbred guinea pigs.

    OpenAIRE

    Cohen, M K; Bartow, R A; Mintzer, C L; McMurray, D. N.

    1987-01-01

    Strain 2 and strain 13 guinea pigs were vaccinated with Mycobacterium bovis BCG and placed on low-protein or protein-adequate diets. Five weeks later all animals were infected by the respiratory route with virulent Mycobacterium tuberculosis H37Rv organisms. Four weeks postchallenge, guinea pigs were skin tested with purified protein derivative and sacrificed. Protein deficiency resulted in significant reductions in body weight and thymus weight and in an impairment in the ability to control ...

  15. Lactoferrin Augmentation of the BCG Vaccine Leads to Increased Pulmonary Integrity

    OpenAIRE

    Actor, Jeffrey K.; Shen-An Hwang; Kruzel, Marian L.; Welsh, Kerry J.

    2011-01-01

    The goal of vaccination to prevent tuberculosis disease (TB) is to offer long-term protection to the individual and the community. In addition, the success of any protective TB vaccine should include the ability to limit cavitary formation and disease progression. The current BCG vaccine protects against disseminated TB disease in children by promoting development of antigenic-specific responses. However, its efficacy is limited in preventing postprimary pulmonary disease in adults that is re...

  16. Application of RAD-BCG calculator to Hanford's 300 area shoreline characterization dataset

    International Nuclear Information System (INIS)

    In 2001, a multi-agency study was conducted to characterize potential environmental effects from radiological and chemical contaminants on the near-shore environment of the Columbia River at the 300 Area of the U.S. Department of Energy's Hanford Site. Historically, the 300 Area was the location of nuclear fuel fabrication and was the main location for research and development activities from the 1940s until the late 1980s. During past waste handling practices uranium, copper, and other heavy metals were routed to liquid waste streams and ponds near the Columbia River shoreline. The Washington State Department of Health and the Pacific Northwest National Laboratory's Surface Environmental Surveillance Project sampled various environmental components including river water, riverbank spring water, sediment, fishes, crustaceans, bivalve mollusks, aquatic insects, riparian vegetation, small mammals, and terrestrial invertebrates for analyses of radiological and chemical constituents. The radiological analysis results for water and sediment were used as initial input into the RAD-BCG Calculator. The RAD-BCG Calculator, a computer program that uses an Excel(regsign) spreadsheet and Visual Basic(regsign) software, showed that maximum radionuclide concentrations measured in water and sediment were lower than the initial screening criteria for concentrations to produce dose rates at existing or proposed limits. Radionuclide concentrations measured in biota samples were used to calculate site-specific bioaccumulation coefficients (Biv) to test the utility of the RAD-BCG-Calculator's site-specific screening phase. To further evaluate site-specific effects, the default Relative Biological Effect (RBE) for internal alpha particle emissions was reduced by half and the program's kinetic/allometric calculation approach was initiated. The subsequent calculations showed the initial RAD-BCG Calculator results to be conservative, which is appropriate for screening purposes.

  17. A Novel Accessory Molecule Trim59 Involved in Cytotoxicity of BCG-Activated Macrophages

    OpenAIRE

    Zhao, Xiangfeng; Liu, Qihui; Du, Baiqiu; Li, Peng; Cui, Qu; Han, Xiao; Du, Bairong; Yan, Dongmei; Zhu, Xun

    2012-01-01

    BCG-activated macrophages (BAM) could kill the tumor cells through cell-cell contact. In this process membrane proteins play an important role. However, up to date, few membrane proteins were revealed. In this study, we selected a surface molecule named Trim59, which was specifically expressed on BAM membrane (compared with the negative control). We cloned and prokaryoticly expressed the extracellular domain of Trim59, purified the recombinant protein and generated polyclonal antibodies. Immu...

  18. Ureteric angioplasty balloon placement to increase localised dosage of BCG for renal pelvis TCC.

    LENUS (Irish Health Repository)

    Forde, J C

    2012-03-01

    Endoscopic percutaneous resection of a renal pelvis transitional cell carcinoma (TCC) is a viable treatment option in those who would be rendered dialysis dependent following a nephroureterectomy. We report endoscopic percutaneous resection of an upper tract TCC recurrence in a single functioning kidney followed by antegrade renal pelvis BCG instillation with novel placement of inflated angioplasty balloon in the ureter to help localise its effect.

  19. Removal of BCG artifacts using a non-Kirchhoffian overcomplete representation

    OpenAIRE

    Dyrholm, Mads; Goldman, Robin; Sajda, Paul; Brown, Truman R.

    2009-01-01

    We present a nonlinear unmixing approach for extracting the ballistocardiogram from EEG recorded in an MR scanner during simultaneous acquisition of fMRI. First, an overcomplete basis is identified in the EEG based on a custom multi-path EEG electrode cap. Next, the overcomplete basis is used to infer non-Kirchhoffian latent variables which are not consistent with a conservative electric field. Neural activity is strictly Kirchhoffian while the BCG artifact is not, and the representation can ...

  20. "PRESUMED SYSTEMIC BACILLE CALMETTE-GUÉRIN DISEASE AFTER BCG VACCINATION: REPORT OF A CLINICAL CASE "

    Directory of Open Access Journals (Sweden)

    P. Tabatabaie

    2006-08-01

    Full Text Available BCG (bacille Calmette–Guérin vaccine is administered worldwide to prevent severe forms of tuberculosis. It is considered to be safe; however, occasional complications are seen. The most serious complication is BCGosis. We report a case of BCGosis with granulomatous hepatitis and acid-fast bacilli in liver and spleen. We treated the patient with antituberculosis drugs without any response to treatment.

  1. Une année d’immersion dans un dispositif de formation aux technologies : prise de conscience du potentiel éducatif des TICE, intentions d’action et changement de pratique

    Directory of Open Access Journals (Sweden)

    Daniel Peraya

    2012-01-01

    Full Text Available [Français] Cette contribution traite des effets d’un dispositif de formation hybride destiné à des étudiants de première année de psychologie et des sciences de l’éducation. La recherche se base sur une analyse qualitative de 66 rapports réflexifs d’étudiants rédigés dans le cadre d’un dispositif dont l’approche pédagogique se veut immersive et située. Cette approche favorise une meilleure compréhension du potentiel des TICE (médiation épistémique ainsi que, dans certains cas, un changement d’attitude par rapport à celles-ci (médiation posturale et, dans d’autres cas, un transfert d’usage à diverses sphères d’activité : académique, professionnelle ou personnelle (médiation praxéologique. [English] This article examines the effects of a specific hybrid learning program, supported by a technology-mediated environment, on first year students enrolled in the Faculty of Psychology and Educational Sciences at the University of Geneva. The study, a qualitative analysis based on 66 students’ selfreflexive reports, suggests that this program, with its situated and immersive pedagogy, promotes a better understanding of the educational potential of ICT (epistemic mediation, a change in attitude towards these technologies (postural mediation and, in some cases, the transfer of use to various spheres of activity : academic, professional and private spheres (praxeological mediation.

  2. Is tuberculin testing before BCG vaccination necessary for children over three months of age?

    LENUS (Irish Health Repository)

    Hennessy, B

    2008-03-01

    In July 2007 Irish national policy changed such that children aged 3 months to 6 years no longer routinely require tuberculin (Mantoux) skin testing prior to BCG vaccination. Previous to that a tuberculin test was required in all children in this age group pre vaccination. While the previous policy was in place this study was conducted to assess the value of this test. The observation that children are frightened by the test (an injection into the skin) prompted the study. The author conducted a retrospective study of the results of 1,854 tuberculin tests performed as a prerequisite to BCG vaccination and found that only 0.7% of children had a positive test result (induration > 5mm). None of 107 children < 6 years of age tested positive. Those > 12 years were more likely to test positive than younger children (1.09% vs 0.4% respectively, p < 0.05). This study suggests that testing young children before BCG vaccination has a low yield of positive results and adds little to the detection of latent or active TB.

  3. Combined BCG and irradiation treatment of skin metastases originating from malignant melanoma

    International Nuclear Information System (INIS)

    Treatment with BCG (Bacillus Calmette-Guerin) followed by irradiation was attempted to improve response to therapy by cutaneous metastases from malignant skin melanomas. Both agents were applied in low doses, known to cause minimal side effects. Nineteen patients, divided into three groups, entered the clinical trial. The first group consisted of five patients with numerous, small skin metastases. The nine patients of the second group presented a small number of relatively large metastases that usually appeared as a residual disease in the surgically treated area. Five patients with numerous, large metastases were included in the third group. The treatment sequence consisted of applying BCG intralesionally in doses from 4 x 105 to 1.17 x 107 viable units. After a free interval, the affected area was irradiated with doses from 1500-2500 ret. Patients with numerous small metastases and those with a small number of larger metastases, i.e., patients of the first and second group, showed a complete response and in these cases regression affected all the noninjected nodules and was also effective when regression could not have been achieved by BCG alone

  4. Comparison of BCG artifact removal methods for evoked responses in simultaneous EEG-fMRI.

    Science.gov (United States)

    Shams, Nasim; Alain, Claude; Strother, Stephen

    2015-04-30

    Simultaneous recording of electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) has gained attention due to the complimentary properties of the two imaging modalities. Their combined recording enables the study of brain function while taking advantage of the high temporal resolution of EEG and high spatial resolution of fMRI. However EEG data recorded inside the MR scanner is significantly contaminated by two main sources of artifacts: MR gradient artifacts and ballistocardiogram (BCG) artifacts. Most existing removal approaches for these artifacts fall into two main categories: average artifact subtraction (AAS) and optimal basis selection (OBS). While these techniques can improve the data quality significantly, highly effective removal of artifacts - particularly the BCG artifact - from the data is still lacking. Here, we compared two of the most commonly used algorithms for BCG artifact removal (OBS and AAS) based on the estimated signal-to-noise ratio (SNR) of auditory and visual evoked responses recorded during fMRI acquisition. We also further compared optimization of OBS for groups, and at the individual subject and run level. The results suggest that performance of the OBS algorithm can be significantly improved by choosing the optimum number of principal components. Furthermore, optimizing the number of principal components at the individual participant and run level results in significant improvements in the SNR of evoked responses compared to group optimization. PMID:25721269

  5. Effects of berberine hydrochloride on CYP450 total content and expression in BCG-induced immune hepatic injury in mice and its possible mechanism

    Institute of Scientific and Technical Information of China (English)

    XinWANG; DanLI; Jun-jieZHANG; Xiu-yunBU; Guo-liangZHANG

    2004-01-01

    AIM:To investigate effects of berberine hydrochloride on hepatic cytochrome P450 in BCG-induced immunological hepatic injury in BALB/c mice and its possible mechanism. METHODS: Immunological liver injury was induced by intravenous injection of Mycobacterium bovis bacillus Calmette-Guerin (BCG, 125 mg/kg) in BALB/c mice. After one week stimulated by BCG,berberine hydrochloride (10, 25, 50, 75, and 100 mg/kg,respectively, qid 7 d) was administrated by intragastric

  6. Disruption of the SapM locus in Mycobacterium bovis BCG improves its protective efficacy as a vaccine against M. tuberculosis

    OpenAIRE

    Festjens, Nele; Bogaert, Pieter; Batni, Anjana; Houthuys, Erica; Plets, Evelyn; Vanderschaeghe, Dieter; Laukens, Bram; Asselbergh, Bob; Parthoens, Eef; De Rycke, Riet; Willart, Monique A.; Jacques, Peggy; Elewaut, Dirk; Brouckaert, Peter; Lambrecht, Bart N.

    2011-01-01

    Mycobacterium bovis bacille Calmette-Guerin (BCG) provides only limited protection against pulmonary tuberculosis. We tested the hypothesis that BCG might have retained immunomodulatory properties from its pathogenic parent that limit its protective immunogenicity. Mutation of the molecules involved in immunomodulation might then improve its vaccine potential. We studied the vaccine potential of BCG mutants deficient in the secreted acid phosphatase, SapM, or in the capping of the immunomodul...

  7. rBCG30-Induced Immunity and Cross-Protection against Mycobacterium leprae Challenge Are Enhanced by Boosting with the Mycobacterium tuberculosis 30-Kilodalton Antigen 85B

    OpenAIRE

    Gillis, Thomas P.; Tullius, Michael V.; Horwitz, Marcus A.

    2014-01-01

    Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimal Mycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine m...

  8. Enhanced Protection against Bovine Tuberculosis after Coadministration of Mycobacterium bovis BCG with a Mycobacterial Protein Vaccine-Adjuvant Combination but Not after Coadministration of Adjuvant Alone▿

    OpenAIRE

    Wedlock, D. Neil; Denis, Michel; Painter, Gavin F; Ainge, Gary D.; Vordermeier, H. Martin; Hewinson, R Glyn; Buddle, Bryce M.

    2008-01-01

    Current efforts are aimed at optimizing the protective efficacy of Mycobacterium bovis BCG by the use of vaccine combinations. We have recently demonstrated that the protection afforded by BCG alone is enhanced by vaccinating cattle with a combination of vaccines comprising BCG and a protein tuberculosis vaccine, namely, culture filtrate proteins (CFPs) from M. bovis plus an adjuvant. In the current study, three different adjuvant systems were compared. The CFP was formulated with a depot adj...

  9. Commonly administered BCG strains including an evolutionarily early strain and evolutionarily late strains of disparate genealogy induce comparable protective immunity against tuberculosis

    OpenAIRE

    Horwitz, Marcus A.; Harth, Günter; Dillon, Barbara Jane; Masleša-Gali, Saša

    2008-01-01

    BCG has been administered to over 4 billion persons worldwide, but its efficacy in preventing tuberculosis in adults has been highly variable. One hypothesis for its variability is that different strains of BCG vary in protective efficacy, and moreover, that evolutionarily early strains are more efficacious than the more attenuated evolutionarily late strains, which lack region of deletion 2. To examine this hypothesis, we tested six widely used BCG strains – the evolutionarily early strain B...

  10. Concomitant Administration of Mycobacterium bovis BCG with the Meningococcal C Conjugate Vaccine to Neonatal Mice Enhances Antibody Response and Protective Efficacy ▿

    OpenAIRE

    Brynjolfsson, Siggeir F.; Bjarnarson, Stefania P.; Mori, Elena; Del Giudice, Giuseppe; Jonsdottir, Ingileif

    2011-01-01

    Mycobacterium bovis BCG is administered to human neonates in many countries worldwide. The objective of the study was to assess if BCG could act as an adjuvant for polysaccharide-protein conjugate vaccines in newborns and thereby induce protective immunity against encapsulated bacteria in early infancy when susceptibility is high. We assessed whether BCG could enhance immune responses to a meningococcal C (MenC) conjugate vaccine, MenC-CRM197, in mice primed as neonates, broaden the antibody ...

  11. Studies of monocytopoiesis in patients with malignant disease and after imunostimulation with BCG, using 3H-thymidine as a DNA-label

    International Nuclear Information System (INIS)

    Monocytopoiesis and blood monocytes were investigated in patients with Hodgkin's disease, non-Hodgkin lymphomas, mycosis fungoides, breast cancer or melanoma. The investigation was carried out before surgery and just before each application of BCG. Monocyte production was increased in untreated patients. Postoperative prophylactic BCG-vaccination gave rise to increased proliferation activity. However monocyte production returned to normal between the 4th and 6th month of BCG immunotherapy. These results indicate that monocytopoiesis is stimulated by human tumors. BCG immunostimulation is able to increase proliferation activity during the first month of treatment only. (orig.)

  12. Inhibition of the Multiplication of Mycobacterium leprae by Vaccination with a Recombinant M. bovis BCG Strain That Secretes Major Membrane Protein II in Mice ▿

    OpenAIRE

    Maeda, Y; Tamura, T.; M. Matsuoka; Makino, M.

    2009-01-01

    The ability of a recombinant Mycobacterium bovis BCG strain that secretes major membrane protein II (MMP-II) of Mycobacterium leprae (BCG-SM) to confer protection against leprosy was evaluated by use of a mouse footpad model. C57BL/6J mice intradermally inoculated with BCG-SM produced splenic T cells which secreted significant amounts of gamma interferon (IFN-γ) in response to either the recombinant MMP-II, the M. leprae-derived membrane fraction, or the BCG-derived cytosolic fraction in vitr...

  13. A new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with higher protective efficacy against tuberculosis.

    Science.gov (United States)

    da Costa, Adeliane Castro; Costa-Júnior, Abadio de Oliveira; de Oliveira, Fábio Muniz; Nogueira, Sarah Veloso; Rosa, Joseane Damaceno; Resende, Danilo Pires; Kipnis, André; Junqueira-Kipnis, Ana Paula

    2014-01-01

    Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that is a major public health problem. The vaccine used for TB prevention is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which provides variable efficacy in protecting against pulmonary TB among adults. Consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of BCG. Here we constructed a new recombinant BCG (rBCG) vaccine expressing a fusion protein (CMX) composed of immune dominant epitopes from Ag85C, MPT51, and HspX and evaluated its immunogenicity and protection in a murine model of infection. The stability of the vaccine in vivo was maintained for up to 20 days post-vaccination. rBCG-CMX was efficiently phagocytized by peritoneal macrophages and induced nitric oxide (NO) production. Following mouse immunization, this vaccine induced a specific immune response in cells from lungs and spleen to the fusion protein and to each of the component recombinant proteins by themselves. Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of lung lesions caused by challenge with Mtb as well as the lung bacterial load. In addition, when this vaccine was used in a prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination. This study describes the creation of a new promising vaccine for TB that we hope will be used in further studies to address its safety before proceeding to clinical trials. PMID:25398087

  14. Is there a correlation between the size of the BCG scar and renal scar of urinary tract infections in children?

    Directory of Open Access Journals (Sweden)

    Salih Kavukçu

    2013-03-01

    Full Text Available Objective: Pyelonephritis cause cellular death, and developmentof scars in kidneys. The aim of this study is todemonstrate a correlation (if any between renal scar, andsize of the scar induced by BCG vaccine in children whohad experienced urinary tract infections. In case of detectionof any correlation, BCG scar formation can be usedas a determinative marker of renal scars, which developfollowing urinary tract infection.Methods: Patients with a history of urinary tract infectionat least 4 months old who had undergone 99mTcDMSAscanning were included in this study. Vertical and horizontaldiameters of BCG scars of the patients in the studygroup were measured. For statistical analysis the greatestdiameter was taken into consideration, and the patientswere divided into 2 subgroups based on the greatest diameterof their BCG scars (Subgroups 1, ≤5 mm, and 2,>5 mm. The patients were also evaluated in 2 groupsas those with (Group 1 or without (Group 2 scars. Bothgroups were compared with subgroups with the largestscar diameters of ≤ 5mm or >5 mmResults: Study population included 108 (82 girls patients.DMSA detected scars in a total of 51 patients.Mean ages of the patients with and without scars were notdifferent (p=0.414. No significant difference was found insize of the BCG scars between renal scar positive andnegative groups (p>0.05.Conclusion: No correlation was found between developmentof renal scar and the size of BCG scar in childrenafter urinary tract infection. J Clin Exp Invest 2013; 4 (1:8-12Key words: BCG scar, renal scar, urinary tract infection,children

  15. Polymorphism in the First Intron of Interferon-Gamma Gene (+874T/A in Patients with BCG Adenitis

    Directory of Open Access Journals (Sweden)

    N Parvaneh

    2009-09-01

    Full Text Available "nBackground: Cytokines and specially interferon-gamma (IFN-g are largely responsible for the regulation of the protective im­mune response against mycobacterial infections. Several studies have clarified the importance of common variants of IFN-g gene regarding the susceptibility to tuberculosis. Bacille Calmette-Guérin (BCG vaccine that is used to prevent se­vere forms of tuberculosis could produce local and systemic side effects. In this study we hypothesized that the IFN-g (+874T/A polymorphism was associated with development of BCG adenitis."nMethods: Thirty patients with BCG adenitis (18 males and 12 females and 30 age and sex-matched healthy children, vacci­nated with BCG during the first two days of life were chosen. All the patients and controls were of Iranian Fars origin and the study was conducted from 2005 to 2007. DNA samples were obtained from 30 patients with BCG adenitis and 30 age and sex matched healthy vaccinees. Polymorphism at +874 was identified using allele specific polymerase chain reac­tion. Allele and genotype frequencies in cases and controls were compared using the χ2 test and odds ratios (OR and their 95% confidence intervals (CI were calculated."nResults: The minor allele (T frequency was significantly lower in patients with BCG adenitis compared to controls (35% vs. 55%, P= 0.02, OR= 0.441, 95% CI= 0.211-0.919. The Armitage trend test revealed a gradually increasing protection from the AA genotype through AT to TT (common odds ratio= 0.49; P= 0.037."nConclusion: Our data suggest that in an Iranian population, the IFN-g (+874T/A polymorphism is associated with develop­ment of BCG adenitis in the vaccinees.

  16. Protection against bovine tuberculosis induced by oral vaccination of cattle with Mycobacterium bovis BCG is not enhanced by co-administration of mycobacterial protein vaccines.

    Science.gov (United States)

    Wedlock, D Neil; Aldwell, Frank E; Vordermeier, H Martin; Hewinson, R Glyn; Buddle, Bryce M

    2011-12-15

    Mycobacterium bovis bacille Calmette-Guérin (BCG) delivered to calves by the oral route in a formulated lipid matrix has been previously shown to induce protection against bovine tuberculosis. A study was conducted in cattle to determine if a combination of a low dose of oral BCG and a protein vaccine could induce protective immunity to tuberculosis while not sensitising animals to tuberculin. Groups of calves (10 per group) were vaccinated by administering 2 × 10(7)colony forming units (CFU) of BCG orally or a combination of 2 × 10(7)CFU oral BCG and a protein vaccine comprised of M. bovis culture filtrate proteins (CFP) formulated with the adjuvants Chitin and Gel 01 and delivered by the intranasal route, or CFP formulated with Emulsigen and the TLR2 agonist Pam(3)CSK(4) and administered by the subcutaneous (s.c.) route. Two further groups were vaccinated with the CFP/Chitin/Gel 01 or CFP/Emulsigen/Pam(3)CSK(4) vaccines alone. Positive control groups were given 10(8)CFU oral BCG or 10(6)CFU s.c. BCG while a negative control group was non-vaccinated. All animals were challenged with M. bovis 15 weeks after vaccination and euthanized and necropsied at 16 weeks following challenge. Groups of cattle vaccinated with s.c. BCG, 10(8)CFU or 2 × 10(7)CFU oral BCG showed significant reductions in seven, three and four pathological or microbiological disease parameters, respectively, compared to the results for the non-vaccinated group. There was no evidence of protection in calves vaccinated with the combination of oral BCG and CFP/Emulsigen/Pam(3)CSK(4) or oral BCG and CFP/Chitin/Gel 01 or vaccinated with the protein vaccines alone. Positive responses in the comparative cervical skin test at 12 weeks after vaccination were only observed in animals vaccinated with s.c. BCG, 10(8)CFU oral BCG or a combination of 2 × 10(7)CFU oral BCG and CFP/Chitin/Gel 01. In conclusion, co-administration of a protein vaccine, administered by either systemic or mucosal routes with oral

  17. Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System.

    Directory of Open Access Journals (Sweden)

    Ting-Yu Angela Liao

    Full Text Available Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine.

  18. Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System.

    Science.gov (United States)

    Liao, Ting-Yu Angela; Lau, Alice; Joseph, Sunil; Hytönen, Vesa; Hmama, Zakaria

    2015-01-01

    Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb) antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine. PMID:26716832

  19. Assisted Living

    Science.gov (United States)

    ... overwhelming majority of residents are female. Assisted Living Philosophy The philosophy of assisted living is to provide personalized, resident ... loved ones to learn about the care provider philosophy . Freedom of Choice The most progressive state regulations ...

  20. Removing ballistocardiogram (BCG) artifact from full-scalp EEG acquired inside the MR scanner with Orthogonal Matching Pursuit (OMP).

    Science.gov (United States)

    Xia, Hongjing; Ruan, Dan; Cohen, Mark S

    2014-01-01

    Ballistocardiogram (BCG) artifact remains a major challenge that renders electroencephalographic (EEG) signals hard to interpret in simultaneous EEG and functional MRI (fMRI) data acquisition. Here, we propose an integrated learning and inference approach that takes advantage of a commercial high-density EEG cap, to estimate the BCG contribution in noisy EEG recordings from inside the MR scanner. To estimate reliably the full-scalp BCG artifacts, a near-optimal subset (20 out of 256) of channels first was identified using a modified recording setup. In subsequent recordings inside the MR scanner, BCG-only signal from this subset of channels was used to generate continuous estimates of the full-scalp BCG artifacts via inference, from which the intended EEG signal was recovered. The reconstruction of the EEG was performed with both a direct subtraction and an optimization scheme. We evaluated the performance on both synthetic and real contaminated recordings, and compared it to the benchmark Optimal Basis Set (OBS) method. In the challenging non-event-related-potential (non-ERP) EEG studies, our reconstruction can yield more than fourteen-fold improvement in reducing the normalized RMS error of EEG signals, compared to OBS. PMID:25120421

  1. A novel recombinant BCG vaccine encoding eimeria tenella rhomboid and chicken IL-2 induces protective immunity against coccidiosis.

    Science.gov (United States)

    Wang, Qiuyue; Chen, Lifeng; Li, Jianhua; Zheng, Jun; Cai, Ning; Gong, Pengtao; Li, Shuhong; Li, He; Zhang, Xichen

    2014-06-01

    A novel recombinant Bacille Calmette-Guerin (rBCG) vaccine co-expressed Eimeria tenella rhomboid and cytokine chicken IL-2 (chIL-2) was constructed, and its efficacy against E. tenella challenge was observed. The rhomboid gene of E. tenella and chIL-2 gene were subcloned into integrative expression vector pMV361, producing vaccines rBCG pMV361-rho and pMV361-rho-IL2. Animal experiment via intranasal and subcutaneous route in chickens was carried out to evaluate the immune efficacy of the vaccines. The results indicated that these rBCG vaccines could obviously alleviate cacal lesions and oocyst output. Intranasal immunization with pMV361-rho and pMV361-rho-IL2 elicited better protective immunity against E. tenella than subcutaneous immunization. Splenocytes from chickens immunized with either rBCG pMV361-rho and pMV361-rho-IL2 had increased CD4(+) and CD8(+) cell production. Our data indicate recombinant BCG is able to impart partial protection against E. tenella challenge and co-expression of cytokine with antigen was an effective strategy to improve vaccine immunity. PMID:25031464

  2. Boosting BCG with inert spores improves immunogenicity and induces specific IL-17 responses in a murine model of bovine tuberculosis.

    Science.gov (United States)

    Garcia-Pelayo, M Carmen; Kaveh, Daryan A; Sibly, Laura; Webb, Paul R; Bull, Naomi C; Cutting, Simon M; Hogarth, Philip J

    2016-05-01

    Tuberculosis (TB) remains a global pandemic, in both animals and man, and novel vaccines are urgently required. Heterologous prime-boost of BCG represents a promising strategy for improved TB vaccines, with respiratory delivery the most efficacious to date. Such an approach may be an ideal vaccination strategy against bovine TB (bTB), but respiratory vaccination presents a technical challenge in cattle. Inert bacterial spores represent an attractive vaccine vehicle. Therefore we evaluated whether parenterally administered spores are efficacious when used as a BCG boost in a murine model of immunity against Mycobacterium bovis. Here we report the use of heat-killed, TB10.4 adsorbed, Bacillus subtilis spores delivered via subcutaneous injection to boost immunity primed by BCG. We demonstrate that this approach improves the immunogenicity of BCG. Interestingly, this associated with substantial boosting of IL-17 responses; considered to be important in protective immunity against TB. These data demonstrate that parenteral delivery of spores represents a promising vaccine vehicle for boosting BCG, and identifies potential for optimisation for use as a vaccine for bovine TB. PMID:27156624

  3. Pre-clinical toxicity and immunogenicity evaluation of a MUC1-MBP/BCG anti-tumor vaccine.

    Science.gov (United States)

    Hu, Boqi; Wang, Juan; Guo, Yingying; Chen, Tanxiu; Ni, Weihua; Yuan, Hongyan; Zhang, Nannan; Xie, Fei; Tai, Guixiang

    2016-04-01

    Mucin 1 (MUC1), as an oncogene, plays a key role in the progression and tumorigenesis of many human adenocarcinomas and is an attractive target in tumor immunotherapy. Our previous study showed that the MUC1-MBP/BCG anti-tumor vaccine induced a MUC1-specific Th1-dominant immune response, simulated MUC1-specific cytotoxic T lymphocyte killing activity, and could significantly inhibit MUC1-expression B16 cells' growth in mice. To help move the vaccine into a Phase I clinical trial, in the current study, a pre-clinical toxicity and immunogenicity evaluation of the vaccine was conducted. The evaluation was comprised of a single-dose acute toxicity study in mice, repeat-dose chronic toxicity and immunogenicity studies in rats, and pilot toxicity and immunogenicity studies in cynomolgus monkeys. The results showed that treatment with the MUC1-MBP/BCG anti-tumor vaccine did not cause any organ toxicity, except for arthritis or local nodules induced by BCG in several rats. Furthermore, the vaccine significantly increased the levels of IFN-γ in rats, indicating that Th1 cells were activated. In addition, the results showed that the MUC1-MBP/BCG anti-tumor vaccine induced a MUC1-specific IgG antibody response both in rats and cynomolgus monkeys. Collectively, these data are beneficial to move the MUC1-MBP/BCG anti-tumor vaccine into a Phase I clinical trial. PMID:26896668

  4. Removing ballistocardiogram (BCG artifact from full-scalp EEG acquired inside the MR scanner with Orthogonal Matching Pursuit (OMP

    Directory of Open Access Journals (Sweden)

    Hongjing eXia

    2014-07-01

    Full Text Available Ballistocardiogram (BCG artifact remains a major challenge that renders electroencephalographic (EEG signals hard to interpret in simultaneous EEG and functional MRI (fMRI data acquisition. Here, we propose an integrated learning and inference approach that takes advantage of a commercial high-density EEG cap, to estimate the BCG contribution in noisy EEG recordings from inside the MR scanner. To estimate reliably the full-scalp BCG artifacts, a near-optimal subset (20 out of 256 of channels first was identified using a modified recording setup. In subsequent recordings inside the MR scanner, BCG-only signal from this subset of channels was used to generate continuous estimates of the full-scalp BCG artifacts via inference, from which the intended EEG signal was recovered. The reconstruction of the EEG was performed with both a direct subtraction and an optimization scheme. We evaluated the performance on both synthetic and real contaminated recordings, and compared it to the benchmark Optimal Basis Set (OBS method. In the challenging non-event-related-potential (non-ERP EEG studies, our reconstruction can yield more than fourteen-fold improvement in reducing the normalized RMS error of EEG signals, compared to OBS.

  5. Screening and Assessing 11 Mycobacterium tuberculosis Proteins as Potential Serodiagnostical Markers for Discriminating TB Patients from BCG Vaccinees

    Institute of Scientific and Technical Information of China (English)

    Guoqiang Zhang; Lingxia Zhang; Mingcheng Zhang; Linlin Pan; Fengyu Wang; Jun Huang; Guoli Li; Jun Yu; Songnian Hu

    2009-01-01

    Purified protein derivative(PPD)skin tests often yield poor specificity, so that to develop new serological antigens for distinguishing between Mycobacterium tu-berculosis infection and Bacille Calmette-Guerin(BCG)vaccination is a priority, especially for developing countries like China. We predicted the antigenicity for selected open reading frames(ORFs)based on the genome sequences of M. tu-berculosis H37Rv and M. bovis BCG, as well as their functions and differences of expression under different stimulus. The candidate ORFs were cloned from H37Rv sequences and expressed as recombinant proteins in Escherichia coll. We studied the serodiagnostic potential of 11 purified recombinants by using enzyme-linked immunosorbent assay(ELISA)and involving a cohort composed of 58 TB patients (34 males and 24 females), 8 healthy volunteers and 50 PPD-negative individuals before and after BCG vaccination. For all the 11 antigens, the median OD val-ues for the sera from TB patients were statistically significantly higher than those for PPD-negative individuals before or after BCG vaccination(P<0.01). They had at least 92% specificity in healthy controls and six seroantigens(Rv0251c, Rv1973, Rv2376c, Rv2537c, Rv2785c and Rv3873A)were never reported with seroantigenicities previously. Thus the approach combining comparative genomies, bioinformatics and ELISA techniques can be employed to identify new seroantigens distinguishing M. tuberculosis infection from BCG vaccination.

  6. Comparative genomics of the Mycobacterium signaling architecture and implications for a novel live attenuated Tuberculosis vaccine.

    Science.gov (United States)

    Zhou, Peifu; Xie, Jianping

    2014-01-01

    Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains a major threat to global public health. A new TB vaccine affording superior immune protection to M. bovis Bacillus Calmette-Guérin (BCG) is imperative. The advantage of a live attenuated vaccine is that it can mimic the bona fide pathogen, elicit immune responses similar to natural infection, and potentially provide more protection than other vaccines. BCG, the only vaccine and a live attenuated vaccine that is the result of cumulative mutations by serial passage of M. bovis, has provided clues for the construction of novel improved vaccines. A strategy is put forward for identifying a new live attenuated TB vaccine generated by cumulative mutation based on M.tb. Given the important role of the M.tb signaling network consisting of a two-component system, eukaryotic-like Ser/Thr protein kinase system and sigma factor system based on comparisons among M.tb H37Rv, M. bovis, and BCG, we have put a premium on this signaling circuit as the starting point for the generation of an attenuated TB vaccine. PMID:24013364

  7. Distribution of 35S-labelled BCG after application to the camera oculi anterior of BCG vaccinated and non-vaccinated rabbits

    International Nuclear Information System (INIS)

    After application of 35S-labelled BCG to the camera oculi anterior of the rabbit, the escape pathways of germs and their quantitative and qualitative distribution in eyes and blood has been studied in BCG-vaccinated and non-vaccinated animals while varying the amount of germs applied. As criteria, 35S concentration and the amount of 35S in ocular sections and in the blood which can be identified by means of distributing germs under the chosen conditions, have been detected. After only 10 minutes, elimination of germs is to be seen, continuing for a period longer than the 2 hours of post-injection period observed. Relatively high 35S concentrations indicate a long-term storage in the iris and in the ciliary body. The flow continues regularly but restrained via choroid and sclera into the blood. Flow velocity depends only within specific limits on the amount of germs injected into the anterior chamber. Under study conditions the flow mode via N.opticus and via lymphs is rather unimportant. The rest of the germs are distributed in the organism via blood vessels. A comparison of 35S concentration in sections of both eyes shows germ enrichment in tissues with sufficient blood supply, particularly in the choroid. Differences in germ distribution in vaccinated and non-vaccinated animals are not to be seen in the 35S distribution pattern. Neither higher nor lower germ doses indicate a stronger retention in the ocular sections of vaccinated animals. The necessity to complete this study by applying germ doses smaller than 1 mg (humidity weight) is stated pointing out technical difficulties involved while applying a test model. (orig.)

  8. Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations

    KAUST Repository

    Abdallah, Abdallah M.

    2015-10-21

    Although Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis have been available for more than 90 years, their effectiveness has been hindered by variable protective efficacy and a lack of lasting memory responses. One factor contributing to this variability may be the diversity of the BCG strains that are used around the world, in part from genomic changes accumulated during vaccine production and their resulting differences in gene expression. We have compared the genomes and transcriptomes of a global collection of fourteen of the most widely used BCG strains at single base-pair resolution. We have also used quantitative proteomics to identify key differences in expression of proteins across five representative BCG strains of the four tandem duplication (DU) groups. We provide a comprehensive map of single nucleotide polymorphisms (SNPs), copy number variation and insertions and deletions (indels) across fourteen BCG strains. Genome-wide SNP characterization allowed the construction of a new and robust phylogenic genealogy of BCG strains. Transcriptional and proteomic profiling revealed a metabolic remodeling in BCG strains that may be reflected by altered immunogenicity and possibly vaccine efficacy. Together, these integrated-omic data represent the most comprehensive catalogue of genetic variation across a global collection of BCG strains.

  9. BCG stimulated dendritic cells induce an interleukin-10 producing T-cell population with no T helper 1 or T helper 2 bias in vitro

    DEFF Research Database (Denmark)

    Madura Larsen, Jeppe; Benn, Christine Stabell; Fillie, Yvonne;

    2007-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine has been associated with beneficial effects on overall childhood mortality in low-income countries; this cannot be explained merely by the prevention of tuberculosis (TB) deaths. The beneficial effects of BCG vaccine could be the result of...

  10. Living Technology

    DEFF Research Database (Denmark)

    2010-01-01

    This book is aimed at anyone who is interested in learning more about living technology, whether coming from business, the government, policy centers, academia, or anywhere else. Its purpose is to help people to learn what living technology is, what it might develop into, and how it might impact...... our lives. The phrase 'living technology' was coined to refer to technology that is alive as well as technology that is useful because it shares the fundamental properties of living systems. In particular, the invention of this phrase was called for to describe the trend of our technology becoming...... increasingly life-like or literally alive. Still, the phrase has different interpretations depending on how one views what life is. This book presents nineteen perspectives on living technology. Taken together, the interviews convey the collective wisdom on living technology's power and promise, as well as its...

  11. New Recombinant Mycobacterium bovis BCG Expression Vectors: Improving Genetic Control over Mycobacterial Promoters.

    Science.gov (United States)

    Kanno, Alex I; Goulart, Cibelly; Rofatto, Henrique K; Oliveira, Sergio C; Leite, Luciana C C; McFadden, Johnjoe

    2016-04-15

    The expression of many antigens, stimulatory molecules, or even metabolic pathways in mycobacteria such asMycobacterium bovisBCG orM. smegmatiswas made possible through the development of shuttle vectors, and several recombinant vaccines have been constructed. However, gene expression in any of these systems relied mostly on the selection of natural promoters expected to provide the required level of expression by trial and error. To establish a systematic selection of promoters with a range of strengths, we generated a library of mutagenized promoters through error-prone PCR of the strong PL5promoter, originally from mycobacteriophage L5. These promoters were cloned upstream of the enhanced green fluorescent protein reporter gene, and recombinantM. smegmatisbacteria exhibiting a wide range of fluorescence levels were identified. A set of promoters was selected and identified as having high (pJK-F8), intermediate (pJK-B7, pJK-E6, pJK-D6), or low (pJK-C1) promoter strengths in bothM. smegmatisandM. bovisBCG. The sequencing of the promoter region demonstrated that it was extensively modified (6 to 11%) in all of the plasmids selected. To test the functionality of the system, two different expression vectors were demonstrated to allow corresponding expression levels of theSchistosoma mansoniantigen Sm29 in BCG. The approach used here can be used to adjust expression levels for synthetic and/or systems biology studies or for vaccine development to maximize the immune response. PMID:26850295

  12. Epidemiological significance of the local reaction to direct BCG vaccination as assessed from a study in Mongolia.

    Science.gov (United States)

    Chavganc, J; Hanák, R; ten Dam, H G

    1969-01-01

    Direct BCG vaccination has considerable operational advantages over the classical method of vaccinating only persons who do not react to tuberculin. In the present study it is shown that the direct method as applied in Mongolia does not cause any untoward reactions in persons who react to tuberculin and therefore can be considered a rational public health procedure.By reason of the repeated follow-up examinations, it was possible to obtain a clear picture of the development of the local BCG reactions and to test the hypothesis that these reactions may give information on pre-existing tuberculin sensitivity. It appeared impossible to deduce with any accuracy from either the local induration or the tissue destruction at the site of vaccination whether a person had tuberculin sensitivity before vaccination or not, and the results obtained with 2 different vaccines were inconsistent. It is therefore concluded that the local BCG reaction has no epidemiological significance in this respect. PMID:5309085

  13. PERBANDINGAN PENGGUNAAN MEDIA OGAWA PUSAT PENELITIAN PENYAKIT MENULAR DAN PERUM. BIO FARMA DALAM TES JUMLAH KUMAN VAKSIN BCG DI JAKARTA

    Directory of Open Access Journals (Sweden)

    Dyah W. Isbagio

    2012-09-01

    Full Text Available The aim of the study was to elaborate factors those might have played a role in the interlaboratory results discrepancies of the quality control for BCG vaccine. One hundred and nineteen samples of commercial BCG vaccine, produced by Bio Farma, had been put into extensive viability tests at Communicable Diseases Research Centre. The tests were done in a pair using Ogawa media prepared both by Bio Farma and by Communicable Diseases Research Centre. The Bio Farma's Ogawa medium revealed an average colony-count values of 1,529 x 106 particles/ ml^ while the Communicable Diseases Research Centre's Ogawa medium gave average figure of 1,504 x 10 particles/ml. As judged by student's paired t test, these results were not statistically significant. Apparently, the media used in the test were not responsible for the discrepancies of results of quality control for BCG vaccine.

  14. Influence of whole body irradiation on BCG contact suppression of a rat sarcoma and tumour-specific immunity

    International Nuclear Information System (INIS)

    An assessment has been made of the influence of host immunosuppression on Bacillus Calmette Guerin (BCG) contact suppression of a syngenetically transplanted, highly immunogenic, 3-methylcholanthrene-induced rat sarcoma. Experiments have been carried out with transplanted cells derived from solid tissue and from an in vitro culture line, the latter excluding the possibility of transfer to immunosuppressed rats of lymphoid cells present in preparations from solid tissue. Normal or whole-body γ-irradiated (450 rad 24 hours before injection) rats were injected s.c. with mixtures of tumour cells and BCG organisms, and some of the animals received a simultaneous challenge of tumour cells alone at a contralateral subcutaneous site. Whole-body irradiation did not abrogate the local suppressive effect of BCG injected in admixture with sarcoma cells, whereas in contrast the development of tumour-specific host immunity, normally occurring concomitantly with rejection of mixed inocula, was totally abrogated by whole-body irradiation. (U.K.)

  15. Enhanced and enduring protection against tuberculosis by recombinant BCG-Ag85C and its association with modulation of cytokine profile in lung.

    Directory of Open Access Journals (Sweden)

    Ruchi Jain

    Full Text Available BACKGROUND: The variable efficacy (0-80% of Mycobacterium bovis Bacille Calmette Guréin (BCG vaccine against adult tuberculosis (TB necessitates development of alternative vaccine candidates. Development of recombinant BCG (rBCG over-expressing promising immunodominant antigens of M. tuberculosis represents one of the potential approaches for the development of vaccines against TB. METHODS/PRINCIPAL FINDINGS: A recombinant strain of BCG - rBCG85C, over expressing the antigen 85C, a secretory immuno-dominant protein of M. tuberculosis, was evaluated for its protective efficacy in guinea pigs against M. tuberculosis challenge by aerosol route. Immunization with rBCG85C resulted in a substantial reduction in the lung (1.87 log(10, p<0.01 and spleen (2.36 log(10, p<0.001 bacillary load with a commensurate reduction in pathological damage, when compared to the animals immunized with the parent BCG strain at 10 weeks post-infection. rBCG85C continued to provide superior protection over BCG even when post-challenge period was prolonged to 16 weeks. The cytokine profile of pulmonary granulomas revealed that the superior protection imparted by rBCG85C was associated with the reduced levels of pro-inflammatory cytokines - interleukin (IL-12, interferon (IFN-gamma, tumor necrosis factor (TNF-alpha, moderate levels of anti-inflammatory cytokine - transforming growth factor (TGF-beta along with up-regulation of inducible nitric oxide synthase (iNOS. In addition, the rBCG85C vaccine induced modulation of the cytokine levels was found to be associated with reduced fibrosis and antigen load accompanied by the restoration of normal lung architecture. CONCLUSIONS/SIGNIFICANCE: These results clearly indicate the superiority of rBCG85C over BCG as a promising prophylactic vaccine against TB. The enduring protection observed in this study gives enough reason to postulate that if an open-ended study is carried out with low dose of infection, rBCG85C vaccine in all

  16. BCG: a computer code for calculating neutron spectra and criticality in cells of fast reactors

    International Nuclear Information System (INIS)

    The BCG code for determining the space and energy neutron flux distribution and criticality of fast reactor cylindrical cells is discussed. The code solves the unidimensional neutron transport equation together with interface current relations at each energy point in an unionized energy grid prepared for the cell and at an arbitrary number of spatial zones. While the spatial resolution is user specified, the energy dependence of the flux distribution is resolved according to the degree of variation in the reconstruced total microscopic cross sections of the atomic species in the cell. Results for a simplified fuel cell illustrate the high resolution and accuracy that can be obtained with the code. (author)

  17. Value of hilar tomography in children with positive tuberculin reaction and not inoculated with BCG

    International Nuclear Information System (INIS)

    X-ray films of the thorax in two levels were prepared of 15 children of 3-14 years of age who had not been BCG-inoculated, after the tuberculin test had shown a positive reaction. Besides bacteriology and bronchoscopy, tomography of the hilus and of the anterior mediastinum was performed to exclude hilar lymph node enlargements. In this manner, it became possible to disclose an enlargement of lymphatic nodes in four children in whom plain radiography of the thorax had not yielded any abnormal findings. (orig.)

  18. BCG Moreau Rio de Janeiro: an oral vaccine against tuberculosis - review

    OpenAIRE

    Thereza Christina Benévolo-de-Andrade; Renata Monteiro-Maia; Catherine Cosgrove; Luiz Roberto R Castello-Branco

    2005-01-01

    The vaccine Bacillus of Calmette Guérin (BCG) was originally developed in France as an oral vaccine against tuberculosis. The oral use of this vaccine was replaced by the parenteral route in almost all countries after the Lubeck disaster. In contrast, Brazil retained the oral delivery of the vaccine until the mid-seventies when it was replaced by the intradermal route. This change in route of delivery was mainly secondary to pressure by medical practitioners based on the poor responses of ora...

  19. BCG: a code for calculating pointwise neutron spectra and criticality in fast reactor cells

    International Nuclear Information System (INIS)

    The BCG code for determining the space and energy neutron flux distribution and criticality of fast reactor cylindrical cells is presented. The code solves the unidimensional neutron transport equation together with interface current relations at each energy in an unionized grid prepared for the cell and at an arbitrary number of spatial zones. While the spatial resolution is user specified, the energy dependence of the flux distribution is resolved according to the degree of variation in the reconstructed total microscopic cross sections of the atomic species in the cell. Results for a defined sample problem illustrate the high resolution and accuracy that can be obtained with the code. (author)

  20. Antigen-specific CD4 T cells are induced after intravesical BCG-instillation therapy in patients with bladder cancer and show similar cytokine profiles as in active tuberculosis.

    Science.gov (United States)

    Elsäßer, Julia; Janssen, Martin W; Becker, Frank; Suttmann, Henrik; Schmitt, Kai; Sester, Urban; Stöckle, Michael; Sester, Martina

    2013-01-01

    Specific T cell immunity in patients with active tuberculosis is associated with a decrease in multifunctionality. However, it is unknown whether cytokine profiles differ in patients with primary infection and those with prior contact. We therefore used intravesical immunotherapy with attenuated live Bacille Calmette-Guérin (BCG) in patients with urothelial carcinoma as a model to characterise the induction of systemic immunity towards purified protein derivate (PPD) and to study whether cytokine profiles differ depending on pre-existing immunity. Eighteen patients with non-muscle invasive bladder cancer were recruited during the BCG-induction course. Fifty-four healthy individuals served as controls. Interferon (IFN)-γ and interleukin (IL)-2 producing PPD-specific CD4 T cells were analysed longitudinally before each instillation using a rapid flow-cytometric whole blood immunoassay. Baseline levels of IFN-γ producing PPD-specific T cells were comparable to controls. T cells showed a 5-fold increase to 0.23% by week 2/3, and further increased 8-fold by week 4/5 (to 0.42%, p=0.0007). Systemic immunity was induced in all patients, although the increase was less pronounced in patients with pre-existing immunity. As in active TB, cytokine profiling during therapy revealed a lower percentage of multifunctional IFN-γ/IL-2 double-positive T cells compared to controls (60.2% vs. 71.9%, p=0.0003). Of note, when comparing patients with and without pre-existing immunity, cytokine profiles in patients with primary immunity were shifted towards IL-2 single producing T cells (p=0.02), whereas those in patients with pre-existing immunity were shifted towards IFN-γ single-positivity (p=0.01). In conclusion, systemic T cell responses were induced after BCG-therapy, and their kinetics and cytokine profile depended on pre-existing immunity. Decreased functionality is a typical feature of specific immunity in both patients with active tuberculosis and BCG-therapy. Among patients

  1. ICM cooling, AGN feedback and BCG properties of galaxy groups-Five properties where groups differ from clusters

    OpenAIRE

    Bharadwaj, V.; Reiprich, T. H.; Schellenberger, G.; Eckmiller, H. J.; Mittal, R; Israel, H.

    2014-01-01

    Using Chandra data for a sample of 26 galaxy groups, we constrained the central cooling times (CCTs) of the ICM and classified the groups as strong cool-core (SCC), weak cool-core (WCC) and non-cool-core (NCC) based on their CCTs. The total radio luminosity of the brightest cluster galaxy (BCG) was obtained using radio catalog data and literature, which was compared to the CCT to understand the link between gas cooling and radio output. We determined K-band luminosities of the BCG with 2MASS ...

  2. Improved protection in guinea pigs after vaccination with a recombinant BCG expressing MPT64 on its surface

    Directory of Open Access Journals (Sweden)

    Simon O. Clark

    2015-01-01

    Full Text Available The lack of an efficient vaccine against tuberculosis is still one of the major problems threatening global human health. In previous work we showed that expression of the protective antigen MPT64 on the surface of Mycobacterium bovis BCG, the only approved vaccine against tuberculosis, strongly improved its immunogenicity and protective potential in mice. In this work we demonstrate that the same recombinant strain is able to induce better protection than wild type BCG also in guinea pigs preventing Mycobacterium tuberculosis dissemination and lung pathology, making this strain a strong candidate for further testing.

  3. Concomitant administration of Mycobacterium bovis BCG with the meningococcal C conjugate vaccine to neonatal mice enhances antibody response and protective efficacy.

    Science.gov (United States)

    Brynjolfsson, Siggeir F; Bjarnarson, Stefania P; Mori, Elena; Del Giudice, Giuseppe; Jonsdottir, Ingileif

    2011-11-01

    Mycobacterium bovis BCG is administered to human neonates in many countries worldwide. The objective of the study was to assess if BCG could act as an adjuvant for polysaccharide-protein conjugate vaccines in newborns and thereby induce protective immunity against encapsulated bacteria in early infancy when susceptibility is high. We assessed whether BCG could enhance immune responses to a meningococcal C (MenC) conjugate vaccine, MenC-CRM(197), in mice primed as neonates, broaden the antibody response from a dominant IgG1 toward a mixed IgG1 and IgG2a/IgG2b response, and increase protective efficacy, as measured by serum bactericidal activity (SBA). Two-week-old mice were primed subcutaneously (s.c.) with MenC-CRM(197). BCG was administered concomitantly, a day or a week before MenC-CRM(197). An adjuvant effect of BCG was observed only when it was given concomitantly with MenC-CRM(197), with increased IgG response (P = 0.002) and SBA (8-fold) after a second immunization with MenC-CRM(197) without BCG, indicating increased T-cell help. In neonatal mice (1 week old) primed s.c. with MenC-CRM(197) together with BCG, MenC-polysaccharide (PS)-specific IgG was enhanced compared to MenC-CRM(197) alone (P = 0.0015). Sixteen days after the second immunization with MenC-CRM(197), increased IgG (P CRM(197) plus BCG showed affinity maturation and detectable SBA (SBA > 128). Thus, vaccination with a meningococcal conjugate vaccine (and possibly with other conjugates) may benefit from concomitant administration of BCG in the neonatal period to accelerate and enhance production of protective antibodies, compared to the current infant administration of conjugate which follows BCG vaccination at birth. PMID:21900528

  4. INTRAVESICULAR IMMUNOTHERAPY WITH BCG VACCINE AND INTERFERON-αα2B FOR NON-INVASIVE CARCINOMA OF THE URINARY BLADDER: RESULTS OF PROSPECTIVE RANDOMIZED STUDY

    Directory of Open Access Journals (Sweden)

    A. A. Minich

    2014-07-01

    Full Text Available Background: Both bacillus Calmette-Gue’rin (BCG and interferon-alpha (IFN-α are active against urinary bladder cancer. In this studywe evaluate the therapeutic efficacy and toxicity of combined intravesical BCG plus IFN-α for treating non-invasive bladder cancer.Subjects and methods: A total of 149 patients (mean age 63.2 years were enrolled for the study. The inclusion criteria were histologically verifiednon-invasive transitional cell carcinoma with intermediate and high risks of recurrence and progression. After transurethral tumor resection, all thepatients were randomized in three groups. Group 1 (n=60 was treated with a 6-week course of BCG, 125 mg, starting 14 to 21 days after TUR, Group2 (n=60 patients received 6-week instillations of BCG, 125 mg, plus IFN-α, 6 million units, Group 3 patients (n = 29 had 4-month courses ofintravesical IFN-α, 6 million units, twice daily during 3 consecutive days. A response was assessed by cystoscopy every 3 months after treatment.Results: A median follow-up of 30.9 months revealed recurrences in 26 (43.3% patients in the BCG group, 8 (13.3% patients in the BCG + IFN-αgroup and 18 (62.1% patients in the IFN-α group. Progression to muscle invasion occurred in 12% and 7% in Groups 1 and 3, respectively, withno progression in Group 2 patients. Three-year relapse-free survival was higher in the BCG+IFN group (78.5% versus 62.6 and 40.2% in theBCG and IFN-α groups, respectively. There was no significant difference between the BCG groups in relapse-free survival. Monotherapy withIFN-α showed a significantly lower response rate than did BCG therapies (p = 0.007. Adverse reactions were observed in 25, 116, and 6.9% ofpatients from Groups 1, 2 and 3, respectively. Toxicity-related withdrawal and treatment delay were similar in both BCG groups. Comparison ofthe rate of adverse reactions revealed a significant difference between the BCG + IFN-α and BCG groups (p = 0.025. The respective rates ofmoderate

  5. Mycobacterium leprae phenolglycolipid-1 expressed by engineered M. bovis BCG modulates early interaction with human phagocytes.

    Directory of Open Access Journals (Sweden)

    Guillaume Tabouret

    Full Text Available The species-specific phenolic glycolipid 1 (PGL-1 is suspected to play a critical role in the pathogenesis of leprosy, a chronic disease of the skin and peripheral nerves caused by Mycobacterium leprae. Based on studies using the purified compound, PGL-1 was proposed to mediate the tropism of M. leprae for the nervous system and to modulate host immune responses. However, deciphering the biological function of this glycolipid has been hampered by the inability to grow M. leprae in vitro and to genetically engineer this bacterium. Here, we identified the M. leprae genes required for the biosynthesis of the species-specific saccharidic domain of PGL-1 and reprogrammed seven enzymatic steps in M. bovis BCG to make it synthesize and display PGL-1 in the context of an M. leprae-like cell envelope. This recombinant strain provides us with a unique tool to address the key questions of the contribution of PGL-1 in the infection process and to study the underlying molecular mechanisms. We found that PGL-1 production endowed recombinant BCG with an increased capacity to exploit complement receptor 3 (CR3 for efficient invasion of human macrophages and evasion of inflammatory responses. PGL-1 production also promoted bacterial uptake by human dendritic cells and dampened their infection-induced maturation. Our results therefore suggest that M. leprae produces PGL-1 for immune-silent invasion of host phagocytic cells.

  6. Assessment of tuberculosis infection during treatment with biologic agents in a BCG-vaccinated pediatric population.

    Science.gov (United States)

    Atikan, Basak Yildiz; Cavusoglu, Cengiz; Dortkardesler, Merve; Sozeri, Betul

    2016-02-01

    Biologic therapies, such as tumor necrosis factor-alpha (TNF-α) blockers, are commonly used to treat rheumatological diseases in childhood. Screening patients for tuberculosis (TB) is highly recommended before starting therapy with TNF-α blockers. Despite appropriate screening, TB still remains a problem in patients receiving anti-TNF therapy in countries where TB is not endemic. TB in anti-TNF-treated patients is often diagnosed late due to altered presentation, and this delay results in high morbidity and mortality with a high proportion of extrapulmonary and disseminated disease. The aim of this study is to show the course of TB disease in children who are on biologic therapy, in an era where many of the children are BCG-vaccinated and TB is intermediately endemic. We recruited 71 patients with several types of inflammatory diseases. Six of them had a positive test result during TB screening and began taking isoniazid (INH) prophylactically. During the 3 years of follow-up, none of these patients developed TB disease. Biologic agents can be safely used in a BCG-vaccinated pediatric population, as long as patients are closely monitored to ensure that any cases of TB will be detected early. PMID:25515621

  7. T-cell activation is an immune correlate of risk in BCG vaccinated infants.

    Science.gov (United States)

    Fletcher, Helen A; Snowden, Margaret A; Landry, Bernard; Rida, Wasima; Satti, Iman; Harris, Stephanie A; Matsumiya, Magali; Tanner, Rachel; O'Shea, Matthew K; Dheenadhayalan, Veerabadran; Bogardus, Leah; Stockdale, Lisa; Marsay, Leanne; Chomka, Agnieszka; Harrington-Kandt, Rachel; Manjaly-Thomas, Zita-Rose; Naranbhai, Vivek; Stylianou, Elena; Darboe, Fatoumatta; Penn-Nicholson, Adam; Nemes, Elisa; Hatheril, Mark; Hussey, Gregory; Mahomed, Hassan; Tameris, Michele; McClain, J Bruce; Evans, Thomas G; Hanekom, Willem A; Scriba, Thomas J; McShane, Helen

    2016-01-01

    Vaccines to protect against tuberculosis (TB) are urgently needed. We performed a case-control analysis to identify immune correlates of TB disease risk in Bacille Calmette-Guerin (BCG) immunized infants from the MVA85A efficacy trial. Among 53 TB case infants and 205 matched controls, the frequency of activated HLA-DR(+) CD4(+) T cells associates with increased TB disease risk (OR=1.828, 95% CI=1.25-2.68, P=0.002, FDR=0.04, conditional logistic regression). In an independent study of Mycobacterium tuberculosis-infected adolescents, activated HLA-DR(+) CD4(+) T cells also associate with increased TB disease risk (OR=1.387, 95% CI=1.068-1.801, P=0.014, conditional logistic regression). In infants, BCG-specific T cells secreting IFN-γ associate with reduced risk of TB (OR=0.502, 95% CI=0.29-0.86, P=0.013, FDR=0.14). The causes and impact of T-cell activation on disease risk should be considered when designing and testing TB vaccine candidates for these populations. PMID:27068708

  8. THE MASS-RICHNESS RELATION OF MaxBCG CLUSTERS FROM QUASAR LENSING MAGNIFICATION USING VARIABILITY

    International Nuclear Information System (INIS)

    Accurate measurement of galaxy cluster masses is an essential component not only in studies of cluster physics but also for probes of cosmology. However, different mass measurement techniques frequently yield discrepant results. The Sloan Digital Sky Survey MaxBCG catalog's mass-richness relation has previously been constrained using weak lensing shear, Sunyaev-Zeldovich (SZ), and X-ray measurements. The mass normalization of the clusters as measured by weak lensing shear is ∼>25% higher than that measured using SZ and X-ray methods, a difference much larger than the stated measurement errors in the analyses. We constrain the mass-richness relation of the MaxBCG galaxy cluster catalog by measuring the gravitational lensing magnification of type I quasars in the background of the clusters. The magnification is determined using the quasars' variability and the correlation between quasars' variability amplitude and intrinsic luminosity. The mass-richness relation determined through magnification is in agreement with that measured using shear, confirming that the lensing strength of the clusters implies a high mass normalization and that the discrepancy with other methods is not due to a shear-related systematic measurement error. We study the dependence of the measured mass normalization on the cluster halo orientation. As expected, line-of-sight clusters yield a higher normalization; however, this minority of haloes does not significantly bias the average mass-richness relation of the catalog.

  9. COSMOLOGICAL CONSTRAINTS FROM THE SLOAN DIGITAL SKY SURVEY MaxBCG CLUSTER CATALOG

    International Nuclear Information System (INIS)

    We use the abundance and weak-lensing mass measurements of the Sloan Digital Sky Survey maxBCG cluster catalog to simultaneously constrain cosmology and the richness-mass relation of the clusters. Assuming a flat ΛCDM cosmology, we find σ8(Ωm/0.25)0.41 = 0.832 ± 0.033 after marginalization over all systematics. In common with previous studies, our error budget is dominated by systematic uncertainties, the primary two being the absolute mass scale of the weak-lensing masses of the maxBCG clusters, and uncertainty in the scatter of the richness-mass relation. Our constraints are fully consistent with the WMAP five-year data, and in a joint analysis we find σ8 = 0.807 ± 0.020 and Ωm = 0.265 ± 0.016, an improvement of nearly a factor of 2 relative to WMAP5 alone. Our results are also in excellent agreement with and comparable in precision to the latest cosmological constraints from X-ray cluster abundances. The remarkable consistency among these results demonstrates that cluster abundance constraints are not only tight but also robust, and highlight the power of optically selected cluster samples to produce precision constraints on cosmological parameters.

  10. Frequency of positive tuberculin skin test in bcg-vaccinated asymptomatic adults in pakistan

    International Nuclear Information System (INIS)

    Objective: To determine the frequency of positive tuberculin skin test (TST) in BCG-vaccinated asymptomatic healthy Pakistani adults. Study Design: Cross sectional study. Place and Duration of Study: The study was carried out in Military Hospital, Rawalpindi in 2008 over six months. Patients and Methods: One hundred and thirty six individuals fulfilling inclusion and exclusion criteria of study were recruited after consent. They were subjected to TST (Mantoux test) and results were interpreted after 72 hours of injection. Test was recorded as positive if the indurated area was > 10 mm, and strongly positive if > 15 mm. Results: All participants were male with the mean age of 26.35+-6.164 years. The overall frequency of positive TST was 41.2%. Out of these, 9.6% were strongly positive. Conclusion: In healthy, BCG-vaccinated adult Pakistani population, TST is found to be positive in high frequency, and even induration of more than 15 mm was seen in significant number. In view of low specificity, TST should not be relied upon for the diagnosis of active tuberculosis (TB). (author)

  11. Mycobacterial Osteomyelitis of the Spine Following Intravesical BCG Therapy for Bladder Cancer.

    Science.gov (United States)

    Mackel, Charles E; Burke, Shane M; Huhta, Taylor; Riesenburger, Ron; Weller, Simcha J

    2016-01-01

    Osteomyelitis is an infection of the bone that can involve the vertebral column. A rare cause of vertebral osteomyelitis is Mycobacterium bovis after intravesical Bacillus Calmette-Guerin (BCG) therapy for transitional cell carcinoma of the bladder. In this report, we describe the case of a 64-year-old male presenting with constitutional symptoms, progressive thoracic kyphosis, and intractable T11 and T12 radiculopathies over the proceeding six months. A CT scan revealed erosive, lytic changes of the T12 and L1 vertebrae with compression of the T12 vertebra. An MRI demonstrated T11-12 osteomyelitis with intervening discitis and extensive paraspinal enhancement with a corresponding hyperintensity on a short tau inversion recovery (STIR) sequence. A needle aspiration grew out Mycobacterial tuberculosis complex that was pansensitive to all antimicrobial agent therapies, except pyrazinamide on culture, a finding consistent with an M. bovis infection. The patient's infection and neurologic compromise resolved after transthoracic T11-12 vertebrectomies with decompression of the spinal cord and nerve roots as well as T10-L1 instrumented fusion and protracted antimicrobial therapy. The epidemiology and natural history of M. bovis osteomyelitis are reviewed and the authors emphasize a mechanism of vertebral inoculation to explain the predilection of M. bovis osteomyelitis in males after intravesical BCG therapy. PMID:27158574

  12. Patient-recognition data-mining model for BCG-plus interferon immunotherapy bladder cancer treatment.

    Science.gov (United States)

    Shah, Shital C; Kusiak, Andrew; O'Donnell, Michael A

    2006-06-01

    Bladder cancer is the fifth most common malignant disease in the United States with an annual incidence of around 63,210 new cases and 13,180 deaths. The cost for providing care for patients with bladder cancer disease is high. Bladder cancer treatment options such as immunotherapy, chemotherapy, radiation therapy, transurethral resection, and cystectomy, are used with varying success rates. In this research, data from a nationwide bacillus Calmette-Gue rin (BCG) plus interferon-alpha (IFN-alpha) immunotherapy clinical trial was considered. Data mining algorithms were used to analyze the effectiveness of immunotherapy treatment and to understand the prominent parameters and their interactions. The extracted knowledge was used to build a patient recognition model for prediction of treatment outcomes. The data was analyzed to understand the impact of various parameters on the treatment outcome. A list of significant parameters such as cumulative tumor size, presence of residual disease, stages of prior bladder cancer, current state of bladder cancer, and the presence of current bladder cancer (T1) is provided. The decision-making approach outlined in the paper supplemented with additional knowledge bases will lead to a comprehensive analytical road map of the BCG/IFN-alpha immunotherapy treatment. It will provide individualized guidelines for each stage of the treatment as well as measure the success of the treatment. PMID:15978568

  13. Outcome after BCG treatment for urinary bladder cancer may be influenced by polymorphisms in the NOS2 and NOS3 genes☆

    Science.gov (United States)

    Ryk, Charlotta; Koskela, Lotta Renström; Thiel, Tomas; Wiklund, N. Peter; Steineck, Gunnar; Schumacher, Martin C.; de Verdier, Petra J.

    2015-01-01

    Purpose Bacillus Calmette-Guérin (BCG)-treatment is an established treatment for bladder cancer, but its mechanisms of action are not fully understood. High-risk non-muscle invasive bladder-cancer (NMIBC)-patients failing to respond to BCG-treatment have worse prognosis than those undergoing immediate radical cystectomy and identification of patients at risk for BCG-failure is of high priority. Several studies indicate a role for nitric oxide (NO) in the cytotoxic effect that BCG exerts on bladder cancer cells. In this study we investigated whether NO-synthase (NOS)-gene polymorphisms, NOS2-promoter microsatellite (CCTTT)n, and the NOS3-polymorphisms-786T>C (rs2070744) and Glu298Asp (rs1799983), can serve as possible molecular markers for outcome after BCG-treatment for NMIBC. Materials and methods All NMIBC-patients from a well-characterized population based cohort were analyzed (n=88). Polymorphism data were combined with information from 15-years of clinical follow-up. The effect of BCG-treatment on cancer-specific death (CSD), recurrence and progression in patients with varying NOS-genotypes were studied using Cox proportional hazard-models and log rank tests. Results BCG-treatment resulted in significantly better survival in patients without (Log rank: p=0.006; HR: 0.12, p=0.048), but not in patients with a long version ((CCTTT)n ≧13 repeats) of the NOS2-promoter microsatellite. The NOS3-rs2070744(TT) and rs1799983(GG)-genotypes showed decreased risk for CSD (Log rank(TT): p=0.001; Log rank(GG): p=0.010, HR(GG): 0.16, p=0.030) and progression (Log rank(TT): p<0.001, HR(TT): 0.05, p=0.005; Log rank(GG): p<0.001, HR(GG): 0.10, p=0.003) after BCG-therapy compared to the other genotypes. There was also a reduction in recurrence in BCG-treated patients that was mostly genotype independent. Analysis of combined genotypes identified a subgroup of 30% of the BCG-treated patients that did not benefit from BCG-treatment. Conclusions Our results suggest that the

  14. Assisted Living

    Science.gov (United States)

    ... may also be higher than in other supported-living environments. Adult Foster Care Foster care homes generally provide ... board, and some help with activities of daily living. This is provided by ... more home-like environment. Regulations for foster care vary by state, and ...

  15. Another vaccine, another story: BCG vaccination against tuberculosis in India, 1948 to 1960 Outra vacina, outra história: a vacinação de BCG contra tuberculose na Índia, 1948 a 1960

    Directory of Open Access Journals (Sweden)

    Niels Brimnes

    2011-02-01

    Full Text Available Through an examination of mass BCG vaccination against tuberculosis in India between 1948 and 1960 this article draws attention to the diversity of the history of vaccination. The features of vaccination campaigns often differed from those of the celebrated campaign to eradicate smallpox. Due to differences between smallpox and tuberculosis as well as between the vaccines developed against them, an analysis of BCG mass vaccination against tuberculosis seems particularly well suited for this purpose. Three points of difference are identified. First, in non-Western contexts BCG vaccination procedures were modified to a greater extent than vaccination against smallpox. Second, tuberculosis lacked the drama and urgency of smallpox and BCG vaccination campaigns suffered more from recruitment problems than did the more "heroic" smallpox eradication campaign. Third, the BCG vaccine was contested in medical circles and was much better suited than the vaccine against smallpox as a vehicle for the articulation of concerns about post-colonial modernization.Através da observação da vacinação em massa de BCG contra a tuberculose na Índia durante os anos de 1948 a 1960, este artigo chama a atenção para a diversidade da história da vacinação. As características das campanhas de vacinação geralmente diferem daquelas celebradas nas campanhas para erradicação da varíola. Devido às diferenças entre a varíola e a turberculose, assim como entre as vacinas desenvolvidas para combater essas doenças, uma análise da vacinação em massa de BCG contra a turberculose parece especialmente bem situada para essa proposta. Três pontos de diferença foram identificados. O primeiro é que em contextos não ocidentais os procedimentos da vacinação de BCG foram modificados em uma extensão maior do que a vacinação contra a varíola. Em segundo lugar, a tuberculose não tinha o drama e a urgência da varíola, e as campanhas de vacinação de BCG

  16. Prova tuberculínica, BCG oral e infecção tuberculosa em crianças menores de 5 anos Tuberculin test, oral BCG vaccine, and tuberculosis infection among children under five years of age

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    Marialda Höfling de Pádua Dias

    1978-12-01

    Full Text Available São relatados os resultados das provas tuberculínicas com PPD Rt23, 2 UT, em crianças menores de um ano e de um a 4 anos, matriculadas na Clínica Pediátrica do Hospital das Clínicas da Faculdade de Medicina da USP, São Paulo, Brasil, no período de 1971 a 1975. Em 665 crianças menores de um ano encontrou-se 3,15% de reatores fracos e 6,62% de reatores fortes e em 1.298 crianças de um a 4 anos, 0,69% de reatores fracos e 5,5% de reatores fortes. Nas mesmas crianças, foram estudadas as relações entre vacinação BCG oral prévia e positividade à prova tuberculínica nos 2 grupos etários considerados e nos quais se obteve a informação de vacinação anterior com BCG oral. Em 575 crianças menores de um ano e 1.113 de um a 4 anos encontrou-se associação positiva entre vacinação BCG oral prévia e positividade à prova tuberculínica. Analisando a relação entre o número de doses de BCG oral prévio e o resultado das provas tuberculínicas pelo método de Goodman, verificou-se que a proporção de crianças que tinham tomado 3 doses e mais de BCG oral e que apresentaram reação forte à prova tuberculínica é significantemente maior que a observada para os não reatores, fato esse não verificado para o grupo de um a 4 anos. Nas crianças que tomaram uma ou duas doses não foram encontradas diferenças estatisticamente significantes.Results of tuberculin reaction from PPD Rt 23, 2UT are reported on children under one year of age and children from one to four years of age who were registered in the Pediatric Clinics of the Hospital das Clinicas of the College of Medicine of the State University of São Paulo. The study was carried out from 1971 through 1975. In a group of 665 children under one year of age, 3.15% were weak reactors while 6.62% were strong reactors, and, in a group of 1298 children between one to four years of age, 0.69% were weak reactors while 5.5% were strong reactors. The relationship between prior BCG oral

  17. The HyVac4 subunit vaccine efficiently boosts BCG-primed anti-mycobacterial protective immunity.

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    Rolf Billeskov

    Full Text Available BACKGROUND: The current vaccine against tuberculosis (TB, BCG, has failed to control TB worldwide and the protective efficacy is moreover limited to 10-15 years. A vaccine that could efficiently boost a BCG-induced immune response and thus prolong protective immunity would therefore have a significant impact on the global TB-burden. METHODS/FINDINGS: In the present study we show that the fusion protein HyVac4 (H4, consisting of the mycobacterial antigens Ag85B and TB10.4, given in the adjuvant IC31® or DDA/MPL effectively boosted and prolonged immunity induced by BCG, leading to improved protection against infection with virulent M. tuberculosis (M.tb. Increased protection correlated with an increased percentage of TB10.4 specific IFNγ/TNFα/IL-2 or TNFα/IL-2 producing CD4 T cells at the site of infection. Moreover, this vaccine strategy did not compromise the use of ESAT-6 as an accurate correlate of disease development/vaccine efficacy. Indeed both CD4 and CD8 ESAT-6 specific T cells showed significant correlation with bacterial levels. CONCLUSIONS/SIGNIFICANCE: H4-IC31® can efficiently boost BCG-primed immunity leading to an increased protective anti-M.tb immune response dominated by IFNγ/TNFα/IL-2 or TNFα/IL2 producing CD4 T cells. H4 in the CD4 T cell inducing adjuvant IC31® is presently in clinical trials.

  18. Advances in the characterization of a proteol iposome derived from Mycobacterium bovis BCG as vaccine candidate against tuberculosis

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    Nadine Alvarez-Cabrera

    2014-12-01

    Full Text Available Despite efforts to eradicate tuberculosis (TB worldwide, this remains a serious health problem. The Bacillus Calmette-Guerin (BCG, the only available vaccine against TB, has variable efficacy and though protects against severe forms of the disease in childhood, has a questionable role in the protection against pulmonary tuberculosis in adults. In recent years, new TB vaccine candidates are being developed using multiple vaccine strategies. Taking into account the antigenic similarity of M. bovis BCG and M. tuberculosis, and the history of the use of proteoliposomes in vaccine formulations, we aimed to study the potentialities of a proteoliposome derived from M. bovis BCG (PLBCG as a potential vaccine candidate against TB. The results demonstrate that a PLBCG was obtained, which was observed by different techniques and that is composed of nanoparticulate vesicles. Additionally, analysis by SDSPAGE followed by Coomassie stained showed the presence of several protein bands on PLBCG whose molecular size may correspond with that reported for M. bovis BCG protein having homology to M. tuberculosis.

  19. VizieR Online Data Catalog: Mass and luminosity of maxBCG galaxies groups (Proctor+, 2015)

    Science.gov (United States)

    Proctor, R. N.; Mendes de Oliveira, C.; Azanha, L.; Dupke, R.; Overzier, R.

    2015-11-01

    Our sample was selected from groups identified in the maxBCG catalogue of Koester et al. (2007, Cat. J/ApJ/660/239). This catalogue was constructed from the SDSS photometric survey using a cluster finding algorithm based on three well-defined properties of galaxies in clusters: spatial clustering, the presence of a "red-sequence" and the presence of a brightest cluster galaxy(BCG) at the centre of the cluster (Koester et al., 2007ApJ...660..221K). Using this method, Koester et al. (2007, Cat. J/ApJ/660/239) identify more than 13000 clusters. Using DR9 of the SDSS-III (Ahn et al., 2012ApJS..203...21A, Cat. V/139), we then selected all the clusters from the maxBCG catalogue that have a BCG with a spectroscopic redshift in the redshift interval z=0.05-0.16 and possessing six or more spectroscopically confirmed members. (1 data file).

  20. The XXL survey XV: Evidence for dry merger driven BCG growth in XXL-100-GC X-ray clusters

    Science.gov (United States)

    Lavoie, S.; Willis, J. P.; Démoclès, J.; Eckert, D.; Gastaldello, F.; Smith, G. P.; Lidman, C.; Adami, C.; Pacaud, F.; Pierre, M.; Clerc, N.; Giles, P.; Lieu, M.; Chiappetti, L.; Altieri, B.; Ardila, F.; Baldry, I.; Bongiorno, A.; Desai, S.; Elyiv, A.; Faccioli, L.; Gardner, B.; Garilli, B.; Groote, M. W.; Guennou, L.; Guzzo, L.; Hopkins, A. M.; Liske, J.; McGee, S.; Melnyk, O.; Owers, M. S.; Poggianti, B.; Ponman, T. J.; Scodeggio, M.; Spitler, L.; Tuffs, R. J.

    2016-08-01

    The growth of brightest cluster galaxies is closely related to the properties of their host cluster. We present evidence for dry mergers as the dominant source of BCG mass growth at z ≲ 1 in the XXL 100 brightest cluster sample. We use the global red sequence, Hα emission and mean star formation history to show that BCGs in the sample possess star formation levels comparable to field ellipticals of similar stellar mass and redshift. XXL 100 brightest clusters are less massive on average than those in other X-ray selected samples such as LoCuSS or HIFLUGCS. Few clusters in the sample display high central gas concentration, rendering inefficient the growth of BCGs via star formation resulting from the accretion of cool gas. Using measures of the relaxation state of their host clusters, we show that BCGs grow as relaxation proceeds. We find that the BCG stellar mass corresponds to a relatively constant fraction 1% of the total cluster mass in relaxed systems. We also show that, following a cluster scale merger event, the BCG stellar mass lags behind the expected value from the Mcluster - MBCG relation but subsequently accretes stellar mass via dry mergers as the BCG and cluster evolve towards a relaxed state.

  1. A Comparative Study on the Effect of BCG-PSN and Thymopeptides on T-lymphocyte Subsets of Normal and Immunosuppressed Mice

    Institute of Scientific and Technical Information of China (English)

    邓云华; 陈映玲; 陈兴平; 李永喜; 周礼义

    2003-01-01

    To compare the effects of polysaccharide nucleic acid fraction of bacillus calmette guerin (BCG-PSN) and thymopeptides on T-lymphocytes of normal and immunosuppressed mice, CD4+ and CD8+ T-lymphocyte subsets of single nucleic cell in thymus, spleen and peripheral blood were detected successively by flow cytometry after application of BCG-PSN and thymopeptides. Meanwhile, CD4+/CD8+ ratio was also calculated. The results showed that both BCG-PSN and thymopeptides could decrease the proportion of CD4+ CD8+ T-lymphocyte subsets in the thymus, at the same time increase CD4+ T-lymphocyte, CD8+ T-lymphocyte proportion in the three tissues.The fluctuation in amplitude was greater in thymopeptides group than that in BCG-PSN group. It is concluded that acting location of thymopeptides is in thymus, its stimulating action is stronger than that of BCG-PSN, while BCG-PSN not only accelerates the differentiation in thymus, but also has some direct stimulation to peripheral CD4+ T-lymphocytes, and can maintain CD4+/CD8+ ratio within normal range. So, BCG-PSN is safer.

  2. Histopathological, immunohistochemical and ultraestructural evaluation of inflammatory response in Arius genus fish under experimental inoculation of BCG

    Directory of Open Access Journals (Sweden)

    Ricardo Yuji Sado

    2008-10-01

    Full Text Available The aim of this study was to evaluate the inflammatory response kinetics after experimental inoculation with BCG in the primitive Arius sp. fish. The BCG was applied through the intramuscular injection in the caudal peduncular region, and the samples were collected for the analyses at days 1, 3, 7, 14, 21, and 33 post-injection. Acute phase inflammatory infiltrate was characterized by the predominant mononuclear cells, intersticial edema, and muscular tissue necrosis. As the inflammatory response evolved, a large number of multinuclear giant cells were formed containing the BCG. These giant cells were positive for the S100 protein at the histochemical analysis, which demonstrate the macrofage activity, confirmed by the ultra-structural analysis showing the lack of the cytoplasmic membrane enveloping the many nuclei within the giant cell. These results led to the conclusion that Arius sp. fish injected with the BCG showed a difuse inflammatory response characterized by a large number of mononuclear cells, absence of granuloma formation, and predominant giant cells.Avaliou-se a cinética da resposta inflamatória induzida experimentalmente com BCG em peixes primitivos pertencentes ao gênero Arius. Os animais foram inoculados com BCG por via intramuscular na região do pedúnculo caudal, sendo realizada a coleta do material nos tempos experimentais de 1, 3, 7, 14, 21 e 33 dias pós-inoculação. A fase aguda da resposta inflamatória se mostrou na forma de infiltrado inflamatório composto predominantemente por células mononucleares, edema intersticial e necrose de tecido muscular. À medida que o processo se desenvolveu, houve formação e aumento no número de células gigantes multinucleadas envolvendo o inóculo. Essas células gigantes, ao exame imunohistoquímico, apresentaram positividade à proteína S100 indicando ação de células macrofágicas, além da ultraestrutura apontar a ausência de membrana citoplasmática entre os in

  3. Systemic BCG immunization induces persistent lung mucosal multifunctional CD4 T(EM cells which expand following virulent mycobacterial challenge.

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    Daryan A Kaveh

    Full Text Available To more closely understand the mechanisms of how BCG vaccination confers immunity would help to rationally design improved tuberculosis vaccines that are urgently required. Given the established central role of CD4 T cells in BCG induced immunity, we sought to characterise the generation of memory CD4 T cell responses to BCG vaccination and M. bovis infection in a murine challenge model. We demonstrate that a single systemic BCG vaccination induces distinct systemic and mucosal populations of T effector memory (T(EM cells in vaccinated mice. These CD4+CD44(hiCD62L(loCD27⁻ T cells concomitantly produce IFN-γ and TNF-α, or IFN-γ, IL-2 and TNF-α and have a higher cytokine median fluorescence intensity MFI or 'quality of response' than single cytokine producing cells. These cells are maintained for long periods (>16 months in BCG protected mice, maintaining a vaccine-specific functionality. Following virulent mycobacterial challenge, these cells underwent significant expansion in the lungs and are, therefore, strongly associated with protection against M. bovis challenge. Our data demonstrate that a persistent mucosal population of T(EM cells can be induced by parenteral immunization, a feature only previously associated with mucosal immunization routes; and that these multifunctional T(EM cells are strongly associated with protection. We propose that these cells mediate protective immunity, and that vaccines designed to increase the number of relevant antigen-specific T(EM in the lung may represent a new generation of TB vaccines.

  4. The mycobacterial DNA-binding protein 1 (MDP1 from Mycobacterium bovis BCG influences various growth characteristics

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    Maurischat Sven

    2008-06-01

    Full Text Available Abstract Background Pathogenic mycobacteria such as M. tuberculosis, M. bovis or M. leprae are characterised by their extremely slow growth rate which plays an important role in mycobacterial virulence and eradication of the bacteria. Various limiting factors influence the generation time of mycobacteria, and the mycobacterial DNA-binding protein 1 (MDP1 has also been implicated in growth regulation. Our strategy to investigate the role of MDP1 in mycobacterial growth consisted in the generation and characterisation of a M. bovis BCG derivative expressing a MDP1-antisense gene. Results The expression rate of the MDP1 protein in the recombinant M. bovis BCG containing the MDP1-antisense plasmid was reduced by about 50% compared to the reference strain M. bovis BCG containing the empty vector. In comparison to this reference strain, the recombinant M. bovis BCG grew faster in broth culture and reached higher cell masses in stationary phase. Likewise its intracellular growth in mouse and human macrophages was ameliorated. Bacterial clumping in broth culture was reduced by the antisense plasmid. The antisense plasmid increased the susceptibility of the bacteria towards Ampicillin. 2-D protein gels of bacteria maintained under oxygen-poor conditions demonstrated a reduction in the number and the intensity of many protein spots in the antisense strain compared to the reference strain. Conclusion The MDP1 protein has a major impact on various growth characteristics of M. bovis BCG. It plays an important role in virulence-related traits such as aggregate formation and intracellular multiplication. Its impact on the protein expression in a low-oxygen atmosphere indicates a role in the adaptation to the hypoxic conditions present in the granuloma.

  5. Cellular immunity confers transient protection in experimental Buruli ulcer following BCG or mycolactone-negative Mycobacterium ulcerans vaccination.

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    Alexandra G Fraga

    Full Text Available BACKGROUND: Buruli ulcer (BU is an emerging infectious disease caused by Mycobacterium ulcerans that can result in extensive necrotizing cutaneous lesions due to the cytotoxic exotoxin mycolactone. There is no specific vaccine against BU but reports show some degree of cross-reactive protection conferred by M. bovis BCG immunization. Alternatively, an M. ulcerans-specific immunization could be a better preventive strategy. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used the mouse model to characterize the histological and cytokine profiles triggered by vaccination with either BCG or mycolactone-negative M. ulcerans, followed by footpad infection with virulent M. ulcerans. We observed that BCG vaccination significantly delayed the onset of M. ulcerans growth and footpad swelling through the induction of an earlier and sustained IFN-γ T cell response in the draining lymph node (DLN. BCG vaccination also resulted in cell-mediated immunity (CMI in M. ulcerans-infected footpads, given the predominance of a chronic mononuclear infiltrate positive for iNOS, as well as increased and sustained levels of IFN-γ and TNF. No significant IL-4, IL-17 or IL-10 responses were detected in the footpad or the DLN, in either infected or vaccinated mice. Despite this protective Th1 response, BCG vaccination did not avoid the later progression of M. ulcerans infection, regardless of challenge dose. Immunization with mycolactone-deficient M. ulcerans also significantly delayed the progression of footpad infection, swelling and ulceration, but ultimately M. ulcerans pathogenic mechanisms prevailed. CONCLUSIONS/SIGNIFICANCE: The delay in the emergence of pathology observed in vaccinated mice emphasizes the relevance of protective Th1 recall responses against M. ulcerans. In future studies it will be important to determine how the transient CMI induced by vaccination is compromised.

  6. Natural variation in immune responses to neonatal Mycobacterium bovis Bacillus Calmette-Guerin (BCG Vaccination in a Cohort of Gambian infants.

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    Chris Finan

    Full Text Available BACKGROUND: There is a need for new vaccines for tuberculosis (TB that protect against adult pulmonary disease in regions where BCG is not effective. However, BCG could remain integral to TB control programmes because neonatal BCG protects against disseminated forms of childhood TB and many new vaccines rely on BCG to prime immunity or are recombinant strains of BCG. Interferon-gamma (IFN-gamma is required for immunity to mycobacteria and used as a marker of immunity when new vaccines are tested. Although BCG is widely given to neonates IFN-gamma responses to BCG in this age group are poorly described. Characterisation of IFN-gamma responses to BCG is required for interpretation of vaccine immunogenicity study data where BCG is part of the vaccination strategy. METHODOLOGY/PRINCIPAL FINDINGS: 236 healthy Gambian babies were vaccinated with M. bovis BCG at birth. IFN-gamma, interleukin (IL-5 and IL-13 responses to purified protein derivative (PPD, killed Mycobacterium tuberculosis (KMTB, M. tuberculosis short term culture filtrate (STCF and M. bovis BCG antigen 85 complex (Ag85 were measured in a whole blood assay two months after vaccination. Cytokine responses varied up to 10 log-fold within this population. The majority of infants (89-98% depending on the antigen made IFN-gamma responses and there was significant correlation between IFN-gamma responses to the different mycobacterial antigens (Spearman's coefficient ranged from 0.340 to 0.675, p = 10(-6-10(-22. IL-13 and IL-5 responses were generally low and there were more non-responders (33-75% for these cytokines. Nonetheless, significant correlations were observed for IL-13 and IL-5 responses to different mycobacterial antigens CONCLUSIONS/SIGNIFICANCE: Cytokine responses to mycobacterial antigens in BCG-vaccinated infants are heterogeneous and there is significant inter-individual variation. Further studies in large populations of infants are required to identify the factors that determine

  7. Healthy Living

    Science.gov (United States)

    ... Environment Kids Health Topics Environment & Health Healthy Living Pollution Reduce, Reuse, Recycle Science – How It Works The ... the Label, Mabel Easy Steps to Better Health! Skin Wise All about an important part of your ...

  8. Curative effect of BCG-polysaccharide nuceic acid on atopic dermatitis in mice

    Institute of Scientific and Technical Information of China (English)

    Liu-Hui Wang; Ying Ye; Yi-Qun Zhang; Tao Xiao

    2014-01-01

    Objective:To explore the effect of bacilli Galmette-Gurin (BCG)-polysaccharide nuceic acid on atopic dermatitis in mice and its mechanism. Methods: Forty NC/Nga mice were selected and randomly divided into Group A (model group), Group B (dexamethasone treatment group), Group C (BCG polysaccharide nucleic acid treatment group) and Group D (control group) with 10 mice in each group. Atopic dermatitis model were constructed by applying 2, 4-dinitrochlorobenzene on the skin of the mice. Mice in Group D were treated with acetone solution (100μL) on the foot pad and abdomen after hair removal at the age of 7 weeks, then on ear skin at the age of 8-13 weeks. For mice in A, B and C groups, 100μL of acetone solution containing 2, 4-dinitrochlorobenzene was applied to the foot pad and the abdomen at the age of 7 weeks, then on ear skins at the age of 8 to 13 weeks. At the age of 7-13 weeks, mice in Group A and Group D were treated with 100μL saline (i.p.);mice were given dexamethasone (0.1 mL/kg, i.p.) every other day for 7 weeks in Group B;mice were treated with BCG polysaccharide nucleic acid (0.5 mg/kg, i.p.) every other day for 7 weeks in Group C. The ear thickness was measured every week and the scratching frequency was recorded 1 times for 10 min a week. The mice were sacrificed after the last administration of drugs. IgE, IL-4, IL-10, IL-12 and IFN-γin the plasma were detected using ELISA, and RT-PCR method was employed to detect the concentrations of IL-4, IL-10, IL-12 and IFN-γproteins. After HE staining, the lesion degree of inflammation in ear tissue was observed microscopically. Results:The ear thickness and scratching frequency of Group A were significantly higher than those in group B, C and D (P0.05);the concentrations of IgE, IL-4 and IL-10 in the plasma and the expression of IL-4, IL-10 mRNA in the spleen tissues of Group A, B and C were all significantly higher than those of Group D (P<0.05);the concentrations of plasma IL-12 and IFN-γ, and spleen

  9. Influence and importance of dacarbazine and BCG in sonography of the liver

    International Nuclear Information System (INIS)

    Basing on results obtained in a group of 30 patients with malignant melanoma, the authors investigated the influence of therapy with cytostatics and of immunotherapy with dacarbazine or BCG, respectively, on the sonographic findings in examination of the liver. In 6 patients, we recorded a larger echo reflex pattern subsequent to therapy, similar to the observations made in diffuse changes in the liver and in the formation of multiple metastases in the liver. This complicated the differential sonographic assessment in respect of excluding multiple liver metastases. Diffuse growth occurred in three patients; we did not observe any extended branches of the portal vein, nor did we see any changes in the biliary tract pattern. (orig.)

  10. Comparison of photometric and weight estimation of Mycobacterium content in homogenous BCG cultures containing Tween 80.

    Science.gov (United States)

    Schuh, V; Sír, J; Galliová, J; Svandová, E

    1966-01-01

    A comparison of the weight and photometric methods of primary assay of BCG vaccine has been made, using a vaccine prepared in albumin-free medium but containing Tween 80. In the weight method, the bacteria were trapped on a membrane filter; for photometry a Pulfrich Elpho photometer and an instrument of Czech origin were used. The photometric results were the more precise, provided that the measurements were made within two days of completion of growth; after this time the optical density of the suspension began to decrease slowly. The lack of precision of the weighing method is probably due to the small weight of culture deposit (which was almost on the limit of accuracy of the analytical balance) and to difficulties in the manipulation of the ultrafilter. PMID:5335458

  11. Intranasal mucosal boosting with an adenovirus-vectored vaccine markedly enhances the protection of BCG-primed guinea pigs against pulmonary tuberculosis.

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    Zhou Xing

    Full Text Available BACKGROUND: Recombinant adenovirus-vectored (Ad tuberculosis (TB vaccine platform has demonstrated great potential to be used either as a stand-alone or a boost vaccine in murine models. However, Ad TB vaccine remains to be evaluated in a more relevant and sensitive guinea pig model of pulmonary TB. Many vaccine candidates shown to be effective in murine models have subsequently failed to pass the test in guinea pig models. METHODS AND FINDINGS: Specific pathogen-free guinea pigs were immunized with BCG, AdAg85A intranasally (i.n, AdAg85A intramuscularly (i.m, BCG boosted with AdAg85A i.n, BCG boosted with AdAg85A i.m, or treated only with saline. The animals were then infected by a low-dose aerosol of M. tuberculosis (M.tb. At the specified times, the animals were sacrificed and the levels of infection in the lung and spleen were assessed. In separate studies, the long-term disease outcome of infected animals was monitored until the termination of this study. Immunization with Ad vaccine alone had minimal beneficial effects. Immunization with BCG alone and BCG prime-Ad vaccine boost regimens significantly reduced the level of M.tb infection in the tissues to a similar extent. However, while BCG alone prolonged the survival of infected guinea pigs, the majority of BCG-immunized animals succumbed by 53 weeks post-M.tb challenge. In contrast, intranasal or intramuscular Ad vaccine boosting of BCG-primed animals markedly improved the survival rate with 60% of BCG/Ad i.n- and 40% of BCG/Ad i.m-immunized guinea pigs still surviving by 74 weeks post-aerosol challenge. CONCLUSIONS: Boosting, particularly via the intranasal mucosal route, with AdAg85A vaccine is able to significantly enhance the long-term survival of BCG-primed guinea pigs following pulmonary M.tb challenge. Our results thus support further evaluation of this viral-vectored TB vaccine in clinical trials.

  12. Living language

    CERN Document Server

    Shuttleworth, John

    2008-01-01

    Living Language 3rd edition' has been devised to meet all the new specifications for AS and A level English Language. The best-selling previous edition has been comprehensively revised to ensure full assessment objectives coverage and fulfilment, and delivery of the new four-unit courses from 2008 onwards. 'Living Language 3rd edition' provides linguistic theory, information and ideas which are easily accessed via supported activities and investigations. The text will actively develop students' skills in reading, listening and responding to an extensive range of text genres and data. Building

  13. Effects of Ganoderma sterols (GS) on hepatic cytochrome P450 in BCG-induced immunological hepatic injury in BALB/c mice

    Institute of Scientific and Technical Information of China (English)

    XinWANG; DanLI; Guo-liangZHANG; Zhi-binLIN

    2004-01-01

    AIM: To investigate effects of Ganoderma sterols (GS) isolated from Ganoderma lucidum (Leyss ex fr) Karst on hepatic cytochrome P450 in BCG-induced immunological hepatic injury in BALB/c mice and its possible mechanism. METHODS: Immunological liver injury was induced by one intravenous injection of BCG (125 mg/kg) in BALB/c mice. One week later, successiveintragastric administration of GS (20, 40, 80 mg/kg, per day) and

  14. Effect of milk fermentation by kefir grains and selected single strains of lactic acid bacteria on the survival of Mycobacterium bovis BCG.

    Science.gov (United States)

    Macuamule, C L S; Wiid, I J; van Helden, P D; Tanner, M; Witthuhn, R C

    2016-01-18

    Mycobacterium bovis that causes Bovine tuberculosis (BTB) can be transmitted to humans thought consumption of raw and raw fermented milk products from diseased animals. Lactic acid bacteria (LAB) used in popular traditional milk products in Africa produce anti-microbial compounds that inhibit some pathogenic and spoilage bacteria. M. bovis BCG is an attenuated non-pathogenic vaccine strain of M. bovis and the aim of the study was to determine the effect of the fermentation process on the survival of M. bovis BCG in milk. M. bovis BCG at concentrations of 6 log CFU/ml was added to products of kefir fermentation. The survival of M. bovis BCG was monitored at 12-h intervals for 72 h by enumerating viable cells on Middlebrook 7H10 agar plates enriched with 2% BD BACTEC PANTA™. M. bovis BCG was increasingly reduced in sterile kefir that was fermented for a period of 24h and longer. In the milk fermented with kefir grains, Lactobacillus paracasei subsp. paracasei or Lactobacillus casei, the viability of M. bovis BCG was reduced by 0.4 logs after 24h and by 2 logs after 48 h of fermentation. No viable M. bovis BCG was detected after 60 h of fermentation. Results from this study show that long term fermentation under certain conditions may have the potential to inactivate M. bovis BCG present in the milk. However, to ensure safety of fermented milk in Africa, fermentation should be combined with other hurdle technologies such as boiling and milk pasteurisation. PMID:26544204

  15. Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System

    OpenAIRE

    Ting-Yu Angela Liao; Alice Lau; Sunil Joseph; Vesa Hytönen; Zakaria Hmama

    2015-01-01

    Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb) antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we deve...

  16. A Replication-Limited Recombinant Mycobacterium bovis BCG Vaccine against Tuberculosis Designed for Human Immunodeficiency Virus-Positive Persons Is Safer and More Efficacious than BCG▿ †

    OpenAIRE

    Tullius, Michael V.; Harth, Günter; Masleša-Galić, Saša; Dillon, Barbara J.; Horwitz, Marcus A.

    2008-01-01

    Tuberculosis is the leading cause of death in AIDS patients, yet the current tuberculosis vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is contraindicated for immunocompromised individuals, including human immunodeficiency virus-positive persons, because it can cause disseminated disease; moreover, its efficacy is suboptimal. To address these problems, we have engineered BCG mutants that grow normally in vitro in the presence of a supplement, are preloadable with supplement to ...

  17. La Matriz BCG (Boston Consulting Group para la Gestión de Publicaciones Periádicas The BCG (Boston Consulting Group matrix for management of periodic publications

    Directory of Open Access Journals (Sweden)

    Mª del Pilar Serrano Gallardo

    2005-11-01

    Full Text Available El marketing documental se ha de encargar de satisfacer las necesidades informativas de los usuarios de forma rentable para ellos y para el centro; para ello se ha de partir de un conjunto de herramientas técnicas que se conocen como el Marketing - Mix, y que abarcan el Producto, el Precio, la Distribución y la Comunicación. Dentro de las herramientas destinadas al producto se encuentra la matriz BCG (Boston Consulting Group, que está orientada a gestión, sobre la base de la situación del producto en el mercado. El objetivo del presente artículo es proponer una matriz BCG para la gestión de una publicación periódica enfermera en nuestro mercado.La matriz BCG se construye con dos variables: el Crecimiento del Mercado y la Tasa Relativa del Mercado, las cuales se han operacionalizado como Media de Crecimiento Anual en el número de suscripciones de tres revistas enfermeras (Rol de Enfermería, Metas de Enfermería y Nursing durante el último quinquenio y Media de Tirada Actual de las tres publicaciones. Se han utilizado datos ofrecidos por la Oficina para el Control de la Difusión (OJD. La matriz BCG puede constituirse como herramienta básica en la gestión de publicaciones, dado que tras determinar la situación del producto, se pueden establecer estrategias que ayuden o favorezcan el mejor posicionamiento posible del producto en el mercado.Documentary marketing has to address the information needs of the users in a manner that is cost-effective not only for them but also for the institution. To do this, a set of technical tools, known as Marketing- Mix, need to be used. These tools include the Product, Price, Distribution and Communication. Within the set of tools used for the Product, we find the BCG matrix (Boston Consulting Group, a tool aimed at the management of the product on the basis of where it is positioned in the market. The objective of this paper is to propose a BCG matrix for the management of a nursing periodic

  18. Valor preditivo do teste tuberculínico padronizado em crianças vacinadas com BCG The predictive value of the standard tuberculin test in BCG-vaccinated children

    Directory of Open Access Journals (Sweden)

    Gilberto Ribeiro Arantes

    1992-08-01

    Full Text Available A aplicabilidade do teste tuberculínico em crianças menores de 5 anos vacinadas com BCG é assunto controvertido. Visando contribuir para esclarecê-lo foi analisado o valor preditivo positivo do teste tuberculínico padronizado em população sob elevada cobertura vacinal e baixa prevalência de infecção tuberculosa. A partir da proporção de reatores fortes em lactentes e escolares vacinados e não vacinados, foram calculadas a razão de declínio da alergia tuberculínica nos vacinados e a razão de crescimento nos não vacinados, o que possibilitou a estimativa dos respectivos valores nas idades intermediárias. A expectativa de falsos-positivos (FP foi então calculada por diferença. Conhecidas a sensibilidade e a especificidade do teste (E=1-FP, a cobertura BCG e a prevalência de infecção, os valores preditivos (para a infecção tuberculosa foram: 1,52%, 4,22%, 8,26%, 14,86% e 23,00%, do primeiro ao quinto ano de vida. Nessas condições, a probabilidade de uma reação forte ser devida ao BCG é grande, especialmente nos dois primeiros anos, o que reduz a aplicabilidade clínica e epidemiológica do teste.The applicability of tuberculin test in children under five years of age, BCG-vaccinated during their first year of life, is a controversial matter. With a view to clarifying the subject the predictive positive value of the test in a region of high BCG coverage and low prevalence of tuberculous infection was analysed. From the proportion of strong reactors among infants and school-age children, vaccinated and not unvaccinated, the declining rate of BCG induced allergy and the increment rate of naturally acquired tuberculin sensitivity between the first and the seventh years of life were calculated. Those calculations allowed for the estimation of the respective values for the intermediate ages. The numbers of false positives to be expected were calculated by difference. Knowing the sensibility and the especificity (1 - FP of

  19. Difference in TB10.4 T-cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Billeskov, Rolf; Grandal, Michael V; Poulsen, Christian;

    2010-01-01

    vaccine Ag, TB10.4, in a recombinant form, or when expressed by the pathogen Mycobacterium tuberculosis (M.tb), or by the current anti-tuberculosis vaccine, Mycobacterium bovis BCG. We showed that BCG and M.tb induced a similar CD4(+) T-cell specific TB10.4 epitope-pattern, which differed completely from...... that induced by recombinant TB10.4. This difference was not due to post-translational modifications of TB10.4 or because TB10.4 is secreted from BCG and M.tb as a complex with Rv0287. In addition, BCG and TB10.4/CAF01 were both taken up by DC and macrophages in vivo, and in vitro uptake experiments...... revealed that both TB10.4 and BCG were transported to Lamp(+)-compartments. BCG and TB10.4 however, were directed to different types of Lamp(+)-compartments in the same APC, which may lead to different epitope recognition patterns. In conclusion, we show that different vectors can induce completely...

  20. [A Case Report of Suspected Tuberculous Granuloma in the Kidney after BCG Perfusion Therapy for Urothelial Carcinoma of the Renal Pelvis].

    Science.gov (United States)

    Kobayashi, Shin; Hori, Junichi; Okazaki, Satoshi; Hashizume, Kazumi; Watanabe, Masaki; Wada, Naoki; Kita, Masafumi; Azumi, Makoto; Iwata, Tatsuya; Matsumoto, Seiji; Kakizaki, Hidehiro

    2016-01-01

    A 66-year-old male patient was referred to our hospital for bilateral renal pelvic tumors. Ureteroscopic biopsy revealed urothelial carcinoma (UC) of low grade (G1) of the renal pelvis. Renal sparing treatment with systemic chemotherapy and percutaneous tumor resection was performed. However, during subsequent follow up, a recurrent tumor was found on the left ureter. After ureteroscopic laser ablation of the tumor, Bacillus Calmette-Guerin (BCG) perfusion therapy (once a week, total 6 weeks) was performed via a single J ureteral catheter with no adverse events. Later, another recurrent recurrence was found on the right ureter, and was managed by ureteroscopic laser ablation followed by BCG perfusion therapy via a single J ureteral catheter. However, the patient developed high fever with chill from the day after initial BCG perfusion therapy on the right side. Although we started antibiotics, high fever continued. Then antituberculous drugs were administered and his condition was improved. Computed tomographic scan revealed a right renal mass 57 mm in diameter, which was consistent with tuberculous granuloma. The tuberculous granuloma persisted despite the continuation of anti-tuberculous drugs. In exceptional cases of upper tract UC such as single kidney and bilateral tumor, BCG perfusion therapy has been used as adjunctive treatment to cure or prevent UC. However, dosages and administration methods of BCG perfusion therapy for upper tract UC still remain to be standardized. Serious adverse events after BCG perfusion therapy require prompt and proper management including the use of anti-tuberculous drugs. PMID:26932332

  1. Pulmonary but Not Subcutaneous Delivery of BCG Vaccine Confers Protection to Tuberculosis-Susceptible Mice by an Interleukin 17-Dependent Mechanism.

    Science.gov (United States)

    Aguilo, Nacho; Alvarez-Arguedas, Samuel; Uranga, Santiago; Marinova, Dessislava; Monzón, Marta; Badiola, Juan; Martin, Carlos

    2016-03-01

    Some of the most promising novel tuberculosis vaccine strategies currently under development are based on respiratory vaccination, mimicking the natural route of infection. In this work, we have compared pulmonary and subcutaneous delivery of BCG vaccine in the tuberculosis-susceptible DBA/2 mouse strain, a model in which parenterally administered BCG vaccine does not protect against tuberculosis. Our data show that intranasally but not subcutaneously administered BCG confers robust protection against pulmonary tuberculosis challenge. In addition, our results indicate that pulmonary vaccination triggers a Mycobacterium tuberculosis-specific mucosal immune response orchestrated by interleukin 17A (IL-17A). Thus, IL-17A neutralization in vivo reduces protection and abrogates M. tuberculosis-specific immunoglobulin A (IgA) secretion to respiratory airways and lung expression of polymeric immunoglobulin receptor induced following intranasal vaccination. Together, our results demonstrate that pulmonary delivery of BCG can overcome the lack of protection observed when BCG is given parenterally, suggesting that respiratory tuberculosis vaccines could have an advantage in tuberculosis-endemic countries, where intradermally administered BCG has inefficient effectiveness against pulmonary tuberculosis. PMID:26494773

  2. Long-Lasting Effects of BCG Vaccination on Both Heterologous Th1/Th17 Responses and Innate Trained Immunity

    DEFF Research Database (Denmark)

    Kleinnijenhuis, Johanneke; Quintin, Jessica; Preijers, Frank; Benn, Christine Stabell; Joosten, Leo A B; Jacobs, Cor; van Loenhout, Joke; Xavier, Ramnik J; Aaby, Peter; van der Meer, Jos W M; van Crevel, Reinout; Netea, Mihai G

    2013-01-01

    We have recently shown that BCG (Bacillus Calmette-Guérin) vaccination in healthy volunteers induces epigenetic reprogramming of monocytes, leading to increased cytokine production in response to nonrelated pathogens for up to 3 months after vaccination. This phenomenon was named 'trained immunity......'. In the present study we assessed whether BCG was able to induce long-lasting effects on both trained immunity and heterologous T helper 1 (Th1) and Th17 immune responses 1 year after vaccination. The production of TNFα and IL-1β to mycobacteria or unrelated pathogens was higher after 2 weeks and 3...... months postvaccination, but these effects were less pronounced 1 year after vaccination. However, monocytes recovered 1 year after vaccination had an increased expression of pattern recognition receptors such as CD14, Toll-like receptor 4 (TLR4) and mannose receptor, and this correlated with an increase...

  3. Factors determining whether the parents accept BCG immunization of the new-born child in a high-income country

    DEFF Research Database (Denmark)

    Thybo Pihl, Gitte; Ammentorp, Jette; Kofoed, Poul-Erik

    . My focus for this project is decision making. Method: During the next year all parents planning to give birth at Kolding Hospital will be offered inclusion in the study . In the 2nd/3rd trimester they will receive a letter with information on the study and afterward the local PhD-students or a...... research assistant will call the families and ask them whether they are willing to participate in the study. After the family have made their choice a structured interview with the families will be conducted. Here we ask about the parents’ age, job and dwelling. As a part of the interview, I will use AM O......' Connors 'Decisional Conflict scale' to compare decisional conflicts for the parents that accept BCG vaccination and parents who do not accept the BCG vaccination of their newborn child....

  4. An oral Mycobacterium bovis BCG vaccine for wildlife produced in the absence of animal-derived reagents.

    Science.gov (United States)

    Cross, Martin L; Lambeth, Matthew R; Aldwell, Frank E

    2009-09-01

    Cultures of Mycobacterium bovis BCG, comprising predominantly single-cell bacilli, were prepared in broth without animal-derived reagents. When formulated into a vegetable-derived lipid matrix, the vaccine was stable in vitro and was immunogenic in vivo upon feeding it to mice. This formulation could be useful for oral vaccination of wildlife against tuberculosis, where concern over transmissible prions may preclude the field use of vaccines containing animal products. PMID:19571109

  5. Alteration of neutrophil function in BCG-treated and non-treated swine after exposure to Salmonella typhimurium.

    Science.gov (United States)

    Coe, N E; Frank, D E; Wood, R L; Roth, J A

    1992-06-01

    Salmonella typhimurium infection in swine causes an enterocolitis followed by a persistent carrier state, but little is known about the mechanisms that allow this organism to colonize and persist in host tissues. Neutrophils provide a first line of defense against invading pathogens such as Salmonella typhimurium. The purpose of this study was to evaluate porcine neutrophil function after in vivo exposure to Salmonella and to determine if the immunomodulator, bacillus Calmette Guerin (BCG), exerts any effect on neutrophil function or on the colonization and persistence of S. typhimurium in the pig. Compared to negative controls, neutrophils from pigs exposed to S. typhimurium exhibited significantly decreased iodination, cytochrome-C reduction, antibody-dependent cell-mediated cytotoxicity, random migration, and chemotaxis (P less than or equal to 0.05). Neutrophil bactericidal activity against S. typhimurium was significantly enhanced. Most of the significant differences were noted in the first two days after exposure to Salmonella. Often the functional alterations were biphasic, peaking again 7-10 days after exposure. BCG alone significantly depressed random migration and cytochrome-C reduction in unstimulated neutrophils. The clinical course, colonization pattern, and persistence of Salmonella were similar between pigs receiving BCG and untreated pigs. These data suggest that S. typhimurium infection causes a depression in oxidative metabolism and motility, yet an increase in overall bactericidal activity against S. typhimurium in circulating porcine neutrophils. It also appears that BCG treatment, as reported here, does not enhance resistance of pigs to S. typhimurium colonization or reduce the number of persistent organisms in the porcine ileum. PMID:1321531

  6. An Oral Mycobacterium bovis BCG Vaccine for Wildlife Produced in the Absence of Animal-Derived Reagents▿

    OpenAIRE

    Cross, Martin L; Lambeth, Matthew R.; Aldwell, Frank E.

    2009-01-01

    Cultures of Mycobacterium bovis BCG, comprising predominantly single-cell bacilli, were prepared in broth without animal-derived reagents. When formulated into a vegetable-derived lipid matrix, the vaccine was stable in vitro and was immunogenic in vivo upon feeding it to mice. This formulation could be useful for oral vaccination of wildlife against tuberculosis, where concern over transmissible prions may preclude the field use of vaccines containing animal products.

  7. BCG: A code for solving the space-dependent slowing-down problem in multiregion cylindrical systems

    International Nuclear Information System (INIS)

    The BCG code to compute pointwise spectra for the slowing-down problem in multiregion cylindrical systems is presented. The code solves a set of balance equations and interface current relations at each energy point in a grid which is the union of the individual total cross section energy grids of the materials in the system and at an arbitrary number of spatial zones. Results for a simplified fast reactor fuel cell illustrate the high resolution that can be obtained with the code

  8. A MaxBCG Catalog of 13,823 Galaxy Clusters from the Sloan Digital Sky Survey

    CERN Document Server

    Koester, B P; Annis, J; Wechsler, R H; Evrard, A; Bleem, L; Becker, M; Johnston, D; Sheldon, E; Nichol, R; Miller, C; Scranton, R; Bahcall, N; Barentine, J; Brewington, H; Brinkmann, J; Harvanek, M; Kleinman, S; Krzesínski, J; Long, D; Nitta, A; Schneider, D; Sneddin, S; Voges, W; York, D; 10.1086/509599

    2008-01-01

    We present a catalog of galaxy clusters selected using the maxBCG redsequence method from Sloan Digital Sky Survey photometric data. This catalog includes 13,823 clusters with velocity dispersions greater than 400 km/s, and is the largest galaxy cluster catalog assembled to date. They are selected in an approximately volume-limited way from a 0.5 Gpc^3 region covering 7500 square degrees of sky between redshifts 0.1 and 0.3. (ABRIGDED)

  9. Curative effect of BCG-polysaccharide nuceic acid on atopic dermatitis in mice

    Institute of Scientific and Technical Information of China (English)

    Liu-Hui; Wang; Ying; Ye; Yi-Qun; Zhang; Tao; Xiao

    2014-01-01

    Objective:To explore the effect of bacilli Galmette-Gurin(BCG)-polysaccharide nuceic acid on atopic dermatitis in mice and its mechanism.Methods:Forty NC/Nga mice were selected and randomly divided into Group A(model group),Group B(dexamethasone treatment group),Group C(BCG polysaccharide nucleic acid treatment group) and Group D(control group) with 10 mice in each group.Atopic dermatitis model were constructed by applying 2,4-dinitrochlorobenzene on the skin of the mice.Mice in Group D were treated with acetone solution(100 μ L) on the foot pad and abdomen after hair removal at the age of 7 weeks.then on ear skin at the age of 8-13 weeks.For mice in A,B and C groups,100 μL of acetone solution containing 2,4-dinitrochlorobenzene was applied to the foot pad and the abdomen at the age of 7 weeks,then on ear skins at the age of8 to 13 weeks.At the age of 7-13 weeks,mice in Group A and Group D were treated with 100 μL saline(i.p.);mice were given dexamethasone(0.1 mL/kg,i.p.) every other day for 7 weeks in Group B;mice were treated with BCG polysaccharide nucleic acid(0.5 mg/kg,i.p.) every other day for7 weeks in Group C.The ear thickness was measured every week and the scratching frequency was recorded 1 times for 10 min a week.The mice were sacrificed after the last administration of drugs,IgE,IL-4,IL-10,IL-I2 and IFN- γ in the plasma were detected using ELISA,and RT-PCR method was employed to detect the concentrations of IL-4,IL-10,IL-12 and IFN- γ proteins.After IIK staining,the lesion degree of inflammation in ear tissue was observed microscopically.Results:The ear thickness and scratching frequency of Group A were significantly higher than those in group B,C and D(P<0.05),and there was no significant difference between Group B and C(P>0.05);the concentrations of IgE,IL-4 and IL-10 in the plasma and the expression of IL-4,IL-10 mRNA in the spleen tissues of Group A,B and C were all significantly higher than those of Group D(P<0.05);the concentrations of

  10. The toxicity of rifampicin polylactic acid nanoparticles against Mycobacterium bovis BCG and human macrophage THP-1 cell line

    Science.gov (United States)

    Erokhina, M.; Rybalkina, E.; Barsegyan, G.; Onishchenko, G.; Lepekha, L.

    2015-11-01

    Tuberculosis is rapidly becoming a major health problem. The rise in tuberculosis incidence stimulates efforts to develop more effective delivery systems for the existing antituberculous drugs while decreasing the side effects. The nanotechnology may provide novel drug delivery tools allowing controlled drug release. Rifampicin is one of the main antituberculous drugs, characterized by high toxicity, and Poly (L-lactic acid) (PLLA) is a biodegradable polymer used for the preparation of encapsulated drugs. The aim of our work was to evaluate the toxicity of rifampicin-PLLA nanoparticles against Mycobacterium bovis BCG using human macrophage THP-1 cell line. Our data demonstrate that rifampicin-PLLA is effective against M. bovis BCG in the infected macrophages. The drug is inducing the dysfunction of mitochondria and apoptosis in the macrophages and is acting as a potential substrate of Pgp thereby modulating cell chemosensitivity. The severity of the toxic effects of the rifampicin-PLLA nanoparticles is increasing in a dose-dependent manner. We suggest that free rifampicin induces death of M. bovis BCG after PLLA degradation and diffusion from phago-lysosomes to cytoplasm causing mitochondria dysfunction and affecting the Pgp activity.

  11. BCG Vaccination Induces Robust CD4+ T Cell Responses to Mycobacterium tuberculosis Complex-Specific Lipopeptides in Guinea Pigs.

    Science.gov (United States)

    Kaufmann, Eva; Spohr, Christina; Battenfeld, Sibylle; De Paepe, Diane; Holzhauser, Thomas; Balks, Elisabeth; Homolka, Susanne; Reiling, Norbert; Gilleron, Martine; Bastian, Max

    2016-03-15

    A new class of highly antigenic, MHC-II-restricted mycobacterial lipopeptides that are recognized by CD4-positive T lymphocytes of Mycobacterium tuberculosis-infected humans has recently been described. To investigate the relevance of this novel class of mycobacterial Ags in the context of experimental bacille Calmette-Guérin (BCG) vaccination, Ag-specific T cell responses to mycobacterial lipid and lipopeptide-enriched Ag preparations were analyzed in immunized guinea pigs. Lipid and lipopeptide preparations as well as complex Ag mixtures, such as tuberculin, mycobacterial lysates, and culture supernatants, all induced a similar level of T cell proliferation. The hypothesis that lipopeptide-specific T cells dominate the early BCG-induced T cell response was corroborated in restimulation assays by the observation that Ag-expanded T cells specifically responded to the lipopeptide preparation. A comparative analysis of the responses to Ag preparations from different mycobacterial species revealed that the antigenic lipopeptides are specific for strains of the M. tuberculosis complex. Their intriguing conservation in pathogenic tuberculous bacteria and the fact that these highly immunogenic Ags seem to be actively released during in vitro culture and intracellular infection prompt the urgent question about their role in the fine-tuned interplay between the pathogen and its mammalian host, in particular with regard to BCG vaccination strategies. PMID:26889044

  12. The Mycobacterium bovis BCG prime-Rv0577 DNA boost vaccination induces a durable Th1 immune response in mice.

    Science.gov (United States)

    Gu, Dongqing; Chen, Wei; Mi, Youjun; Gong, Xueli; Luo, Tao; Bao, Lang

    2016-04-01

    Tuberculosis remains a major global health problem and effective vaccines are urgently needed. In this study, we used the combined DNA- and protein-based vaccines of immunodominant antigen Rv0577 to boost BCG and evaluated their immunogenicity in BALB/c mice. Our data suggest that the booster vaccine may substantially enhance the immunogenicity of BCG and strengthen both CD4+ T cell-mediated Th1 and CD8+ T cell-mediated cytolytic responses. Compared with the protein-based vaccine, the DNA-based vaccine can induce more durable Th1 immune response, characterized by high levels of antibody response, proliferation response, percentages of CD4+/CD8+ and cytokine secretion in antigen-stimulated splenocyte cultures. In conclusion, we for the first time, developed a protein- and plasmid DNA-based booster vaccine based on Rv0577. Our findings suggest that antigen Rv0577-based DNA vaccine is immunogenic and can efficiently boost BCG, which could be helpful in the design of an efficient vaccination strategy against TB. PMID:26922320

  13. Does Neutrophil-to-Lymphocyte Ratio Has a Value in Predicting BCG Recurrence in Bladder Tumor Patients

    Directory of Open Access Journals (Sweden)

    Ahmet Camtosun

    2016-01-01

    Full Text Available Aim: To evaluate the prognostic value of preoperative neutrophil to lymphocyte ratio after intravesical Bacillus Calmette-Guérin (BCG treatment in non-muscle-invasive bladder cancer (NMIBC. Material and Method: The data of 70 patients, operated for urothelial carcinoma and treated with BCG after the diagnose of NMIBC at Türkiye Yüksek Ižhtisas Hastanesi between 2007-2013, were reviewed retrospectively. Patients’ preoperative complete blood counter results and first cystoscopic examination findings were recorded.Results: Median follow-up was 26 months. Tumor recurrence was identified at 26 patients (Group 2 among the 70 patients. In 44 patients there was no tumor recurrence (Group 1.  Neutrophil/lyphocyte ratio, multiplicity of tumor and cis frequency were increased statistically in Group 2 (P=0.001, P=0.005, P=0.007, respectively. Discussion: This study showed that, preoperative high neutrophil/lyphocyte ratio, multiplicity of tumor and cis precence can be used as independent criterias for predicting tumor recurrence after intravesical Bacillus Calmette-Guérin (BCG treatment in NMIBC.

  14. ICM cooling, AGN feedback and BCG properties of galaxy groups-Five properties where groups differ from clusters

    CERN Document Server

    Bharadwaj, V; Schellenberger, G; Eckmiller, H J; Mittal, R; Israel, H

    2014-01-01

    Using Chandra data for a sample of 26 galaxy groups, we constrained the central cooling times (CCTs) of the ICM and classified the groups as strong cool-core (SCC), weak cool-core (WCC) and non-cool-core (NCC) based on their CCTs. The total radio luminosity of the brightest cluster galaxy (BCG) was obtained using radio catalog data and literature, which was compared to the CCT to understand the link between gas cooling and radio output. We determined K-band luminosities of the BCG with 2MASS data, and used it to constrain the masses of the SMBH, which were then compared to the radio output. We also tested for correlations between the BCG luminosity and the overall X-ray luminosity and mass of the group. The observed cool-core/non-cool-core fractions for groups are comparable to those of clusters. However, notable differences are seen. For clusters, all SCCs have a central temperature drop, but for groups, this is not the case as some SCCs have centrally rising temperature profiles. While for the cluster sampl...

  15. Medroxyprogesterone acetate alters Mycobacterium bovis BCG-induced cytokine production in peripheral blood mononuclear cells of contraceptive users.

    Directory of Open Access Journals (Sweden)

    Léanie Kleynhans

    Full Text Available Most individuals latently infected with Mycobacterium tuberculosis (M.tb contain the infection by a balance of effector and regulatory immune responses. This balance can be influenced by steroid hormones such as glucocorticoids. The widely used contraceptive medroxyprogesterone acetate (MPA possesses glucocorticoid activity. We investigated the effect of this hormone on immune responses to BCG in household contacts of active TB patients. Multiplex bead array analysis revealed that MPA demonstrated both glucocorticoid and progestogenic properties at saturating and pharmacological concentrations in peripheral blood mononuclear cells (PBMCs and suppressed antigen specific cytokine production. Furthermore we showed that PBMCs from women using MPA produced significantly lower levels of IL-1α, IL-12p40, IL-10, IL-13 and G-CSF in response to BCG which corresponded with lower numbers of circulating monocytes observed in these women. Our research study is the first to show that MPA impacts on infections outside the genital tract due to a systemic effect on immune function. Therefore MPA use could alter susceptibility to TB, TB disease severity as well as change the efficacy of new BCG-based vaccines, especially prime-boost vaccine strategies which may be administered to adult or adolescent women in the future.

  16. Adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine in new-born infants-an evaluation of the Danish strain 1331 SSI in a randomized clinical trial

    DEFF Research Database (Denmark)

    Nissen, Thomas Nørrelykke; Birk, Nina Marie; Kjærgaard, Jesper;

    2016-01-01

    OBJECTIVE: To evaluate adverse reactions of the Bacillus Calmette-Guérin (BCG) Statens Serum Institut (SSI) (Danish strain 1331) used as intervention in a randomized clinical trial. DESIGN: A randomized clinical multicenter trial, The Danish Calmette Study, randomizing newborns to BCG or no inter......OBJECTIVE: To evaluate adverse reactions of the Bacillus Calmette-Guérin (BCG) Statens Serum Institut (SSI) (Danish strain 1331) used as intervention in a randomized clinical trial. DESIGN: A randomized clinical multicenter trial, The Danish Calmette Study, randomizing newborns to BCG...

  17. Insufficient Living

    DEFF Research Database (Denmark)

    Rasmussen, Trine Bernholdt; Zwisler, Ann-Dorthe; Moons, Philip;

    2015-01-01

    a persisting weakness and felt frustrated about the prolonged recovery phase. In "the road to recovery," support from relatives and healthcare professionals, as well as one's own actions, was emphasized as important in facilitating recovery. CONCLUSIONS:: Recovery after IE is perceived as "Insufficient Living...... AND METHODS:: Within a phenomenological-hermeneutical framework, a qualitative interview study was conducted that included 6 men and 5 women (aged 29-86 years). Patients were interviewed 3 to 6 months after discharge. Analysis consisted of 3 levels: naive reading, structured analysis, and critical...

  18. HI in XMD Galaxies III. GMRT observations of BCG HS0822+3542

    CERN Document Server

    Chengalur, J N; Martin, J M; Kniazev, A Yu; Chengalur, Jayaram N.

    2006-01-01

    We present Giant Metrewave Radio Telescope (GMRT) HI 21-cm line data for the smallest known eXtremely Metal Deficient (XMD) blue compact galaxy (BCG) HS0822+3542. From HST imaging it has been suggested that HS0822+3542 actually consists of two still smaller (~ 100pc sized) ultra-compact dwarfs that are in the process of merging. The brighter of these two putative ultra compact dwarfs has an ocular appearance, similar to that seen in galaxies that have suffered a penetrating encounter with a smaller companion. From our HI imaging we find that the gas distribution and kinematics in this object are similar to that of other low mass galaxies, albeit with some evidence for tidal disturbance. On the other hand, the HI emission has an angular size ~25 times larger than that of the putative ultra-compact dwarfs. The optical emission is also offset from the centre of the HI emission. HS0822+3542 is located in the Lynx-Cancer void, but has a nearby companion LSB dwarf galaxy SAO0822+3545. In light of all this we also c...

  19. Cosmological Constraints from the Large Scale Weak Lensing of SDSS MaxBCG Clusters

    CERN Document Server

    Zu, Ying; Rozo, Eduardo; Sheldon, Erin S; Tinker, Jeremy L; Becker, Matthew R

    2012-01-01

    We derive constraints on the matter density \\Om and the amplitude of matter clustering \\sig8 from measurements of large scale weak lensing (projected separation R=5-30\\hmpc) by clusters in the Sloan Digital Sky Survey MaxBCG catalog. The weak lensing signal is proportional to the product of \\Om and the cluster-mass correlation function \\xicm. With the relation between optical richness and cluster mass constrained by the observed cluster number counts, the predicted lensing signal increases with increasing \\Om or \\sig8, with mild additional dependence on the assumed scatter between richness and mass. The dependence of the signal on scale and richness partly breaks the degeneracies among these parameters. We incorporate external priors on the richness-mass scatter from comparisons to X-ray data and on the shape of the matter power spectrum from galaxy clustering, and we test our adopted model for \\xicm against N-body simulations. Using a Bayesian approach with minimal restrictive priors, we find \\sig8(\\Om/0.325...

  20. Identification and characterization of the BCG cell wall-stimulated suppressor cells in inbred rats

    International Nuclear Information System (INIS)

    In vitro experiments were undertaken to investigate the effect of intraperitoneal (i.p.) inoculation of BCG cell walls attached to oil droplets (BCGcw) on mitogenic and alloantigenic responses of spleen and bone marrow cells. These in vitro studies demonstrated that: (1) spleen cells from BCGcw-immunized ACI rats had decreased responsiveness to Concanavalin A (Con A) and to alloantigenic stimulation, (2) depressed Con A reactivity could also be induced in Buffalo rat spleen cells by the i.p. inoculation of BCGcw, (3) normal ACI rats had suppressor cells in their bone marrow but not in their spleens, (4) BCGcw-immunized ACI rats demonstrated an increase in the suppressive activity of their bone marrow as early as 1 day after inoculation of BCGcw, while suppressor activity was found in the spleen as early as 2 days after BCGcw inoculation, (5) characterization of the BCGcw-induced splenic suppressor cell demonstrated it to be adherent to plastic or nylon wool, radiation-resistant, and removed by treatment with carbonyl iron. These properties were consistent with the identification of the suppressor cell as a macrophage, (6) the Con A and mixed lymphocyte reactivities of normal spleen cells could be suppressed by the addition of the adherent spleen cell population from BCGcw-immunized ACI rats, and (7) the adherent suppressor cell from BCGcw-immunized rats suppressed Con A reactivity across a major histocompatability barrier. (Auth.)

  1. Every BCG with a strong radio AGN has an X-ray cool core

    CERN Document Server

    Sun, Ming

    2009-01-01

    Radio AGN feedback in cool cores has been proposed as a crucial ingredient in the evolution of baryonic structures. However, it has long been known that strong radio AGN also exist in noncool core clusters, which brings up the question whether a cool core is always required for radio feedback. In this work, we present a systematic analysis of BCGs and strong radio AGN in 145 groups and clusters from the Chandra archive. All 65 BCGs with radio AGN more luminous than 2x10^23 W Hz^-1 at 1.4 GHz are found to have X-ray cool cores. The BCG cool cores can be divided into two classes, the large-cool-core (LCC) class and the corona class. Small coronae, easily overlooked at z>0.1, can trigger strong heating episodes in groups and clusters, long before large cool cores are formed. Strong radio outbursts triggered by coronae may destroy embryonic large cool cores and thus provide another mechanism to prevent formation of large cool cores. However, it is unclear whether coronae are decoupled from the radio feedback cycl...

  2. Asociación entre tuberculosis infantil grave e inmunización previa con BCG en un hospital de referencia nacional, Perú 1990-2000 Association between severe tuberculosis in children and previous BCG immunization in a national referral Hospital, Peru 1990-2000

    Directory of Open Access Journals (Sweden)

    Félix Llanos-Tejada

    2012-03-01

    Full Text Available El objetivo del estudio fue determinar la asociación entre la inmunización con BCG y tuberculosis grave (TB. Se realizó un estudio retrospectivo, se incluyó fichas de pacientes atendidos en el servicio de neumología del Instituto Nacional de Salud del Niño de Perú, entre los años 1990-2000. Se revisaron un total de 2106 casos de TB entre los que había 259 casos graves (TB miliar o meningoencefalitis por TB. Del total, 497 casos no tenían antecedente de inmunización con BCG; 202 tenían TB grave y 295 TB no grave (OR= 0,05; IC 95%= 0,03-0,07. En conclusión, los niños con diagnóstico de TB y que han sido inmunizados con BCG, tienen 94% menos riesgo de desarrollar TB grave, en comparación a los niños con diagnóstico no inmunizados con BCG.The objective of the study was to determine the association between BCG immunization and severe tuberculosis (TB. We performed a retrospective study, including medical records from patients of the pneumology department at the National Children’s Institute in Peru, between the years 1990-2000. A total of 2106 TB cases were reviewed, from them 259 patients were severe (miliary TB or meningoencephalitic TB. From all, 497 cases did not have history of BCG vaccination, 202 had severe TB and 295 non-severe TB (OR = 0.05, 95% CI = 0.03 to 0.07. In conclusion, children diagnosed with TB and who have been immunized with BCG, has 94% lower risk of developing severe TB, compared to children with TB non-immunized with BCG.

  3. Living Lands

    DEFF Research Database (Denmark)

    Christensen, Suna Møller

    2014-01-01

    , hunters attended to questions like safe-journeying on ice or the role of natural surroundings in children’s education, in ways revealing a relational perception of ‘nature’ and dissolving culture-nature dualisms. Hunters’ experiences in living the land afforded children a dwelling position from which to...... grow with the features of the land. Framed this way, ‘nature’ was regarded as part of the social world. I suggest that learning among Arctic hunters is social and twofold. First, we can learn how human-environment relations influence individual life trajectories. Secondly, ‘nature’ as part of the...... social world pushes questions about education and life, disregarding being educated as human control of nature....

  4. Serviced Living

    Institute of Scientific and Technical Information of China (English)

    LIU BO

    2006-01-01

    @@ As recently as ten years ago,the term serviced apartment made no sense to most people living in Beijing and residing in hotels was the only options for foreign visitors. But since then, serviced apartments have begun to appear in big cities all around China. In Beijing alone, it is estimated that there are more than 30,000service apartments spread across dozens of properties occupying a space of more than I million square meters. Concentrating in the Financial Street, the Central Business District and Zhongguancun, also known as China's Silicon Valley, the explosion in service apartments in the city continues to be fueled by the influx of overseas and domestic business people.

  5. Cell wall lipids from Mycobacterium bovis BCG are inflammatory when inoculated within a gel matrix: characterization of a new model of the granulomatous response to mycobacterial components.

    Science.gov (United States)

    Rhoades, Elizabeth R; Geisel, Rachel E; Butcher, Barbara A; McDonough, Sean; Russell, David G

    2005-05-01

    The chronic inflammatory response to Mycobacterium generates complex granulomatous lesions that balance containment with destruction of infected tissues. To study the contributing factors from host and pathogen, we developed a model wherein defined mycobacterial components and leukocytes are delivered in a gel, eliciting a localized response that can be retrieved and analysed. We validated the model by comparing responses to the cell wall lipids from Mycobacterium bovis bacillus Calmette-Guerin (BCG) to reported activities in other models. BCG lipid-coated beads and bone marrow-derived macrophages (input macrophages) were injected intraperitoneally into BALB/c mice. Input macrophages and recruited peritoneal exudate cells took up fluorescently tagged BCG lipids, and matrix-associated macrophages and neutrophils produced tumor necrosis factor, interleukin-1alpha, and interleukin-6. Leukocyte numbers and cytokine levels were greater in BCG lipid-bearing matrices than matrices containing non-coated or phosphatidylglycerol-coated beads. Leukocytes arrived in successive waves of neutrophils, macrophages and eosinophils, followed by NK and T cells (CD4(+), CD8(+), or gammadelta) at 7 days and B cells within 12 days. BCG lipids also predisposed matrices for adherence and vascularization, enhancing cellular recruitment. We submit that the matrix model presents pertinent features of the murine granulomatous response that will prove to be an adaptable method for study of this complex response. PMID:15850754

  6. Surfactantes reativos não-iônicos em polimerização em emulsão de látices de acetato de vinila - vinil neodecanoato: influência nas propriedades de barreira à água Nonionic reactive surfactants in emulsion polymerization of vinyl acetate - vinyl neodecanoate latexes: influence on the water barrier properties

    Directory of Open Access Journals (Sweden)

    Jorge M. de Oliveira

    2009-01-01

    Full Text Available A indústria de tintas é grande consumidora de látex obtido por polimerização em emulsão. Os surfactantes, essenciais à estabilidade do látex, exercem papel fundamental na produção e na aplicação destes polímeros. Contudo, podem também produzir efeitos adversos nas propriedades do produto, em razão de sua adsorção física às partículas de polímero. Os surfactantes não ligados podem migrar através do filme para as interfaces, formando agregados que podem aumentar a sensibilidade à água, afetando desta forma as propriedades de barreira. Um caminho promissor para minimizar este efeito dos surfactantes convencionais tem sido o uso de surfactantes polimerizáveis, ou reativos, que estão covalentemente ligados ao polímero e, desta forma, não podem ser dessorvidos e migrarem durante a formação do filme. Neste trabalho foram preparados látices de acetato de vinila - vinil neodecanoato (VeoVa 10®, estabilizados com surfactantes não-iônicos convencionais e reativos, e avaliado o desempenho dos filmes obtidos a partir destes látices. Os resultados demonstraram que o uso de surfactantes não-iônicos polimerizáveis pode, sob determinadas condições, trazer ganhos para as propriedades de barreira.The paint industry is a huge consumer of latex from emulsion polymerization. The surfactants, essential to the stability of the latex, play a crucial role in the production and application of emulsion polymers. However, they can also have adverse effects on product properties due to their physical adsorption on the polymer particles. The unbound surfactants can migrate through the film toward the interfaces forming aggregates which increase water sensitivity of the film, thus affecting its barrier properties. A promising way to reduce the negative effects of the conventional surfactants is to use polymerizable or reactive surfactants (surfmers that are covalently linked to the polymer, which avoids its desorption and migration

  7. Pour une nouvelle approche de l'hispanité grâce aux TICE - La formation d'enseignants d'espagnol langue étrangère Towards a new approach of Hispanic culture thanks to ICT - Beginners training for Spanish language teachers

    Directory of Open Access Journals (Sweden)

    Veronique Pugibet

    2006-04-01

    Full Text Available Si désormais les divers pays et cultures du monde hispanique figurent dans les programmes officiels de l'apprentissage de l'espagnol langue étrangère en France, l'approche qui en est proposée demeure encore souvent traditionnelle, une certaine vision de l'histoire et les "beaux" textes dominant largement. Comment amener les jeunes enseignants en formation initiale à porter un regard différent sur l'autre, à atteindre une véritable compétence culturelle dépassant la culture académique ? Nous rendrons compte dans notre étude de la spécificité de la formation initiale des professeurs d'espagnol qui, dorénavant, sont de plus en plus nombreux à être d'origine hispanophone. Nous exposerons leur parcours de formation sur et grâce aux TICE afin de dépasser les clichés réducteurs initiaux comme en témoignent leur approche première sur Internet, et en vue d'atteindre un regard plus ouvert sur l'hispanité et des pratiques pédagogiques différentes.Despite the ongoing presence of several Hispanic countries and cultures in state programs concerning Spanish as a foreign language in French education, the suggested methodology remains very often traditional with a predominantly biased vision of history as well as texts that are considered "beautiful". How can we help young teachers in their initial training to have a different perception of the other, to reach a true cultural competence that surpasses academic culture? We will show in our study the details involved in a Spanish teacher's initial training since, as it appears, they tend to be more and more of Hispanic origin. We will describe their training history through and thanks to the TICE in order to overcome the reductive and stereotyping clichés as they move initially towards the use of Internet, and in order to reach out for a more open perception of the Hispanic World and of different pedagogical practices.

  8. La Matriz BCG (Boston Consulting Group) para la Gestión de Publicaciones Periádicas The BCG (Boston Consulting Group) matrix for management of periodic publications

    OpenAIRE

    Mª del Pilar Serrano Gallardo; Mª Pilar Arroyo Gordo; Ana Mª Giménez Maroto

    2005-01-01

    El marketing documental se ha de encargar de satisfacer las necesidades informativas de los usuarios de forma rentable para ellos y para el centro; para ello se ha de partir de un conjunto de herramientas técnicas que se conocen como el Marketing - Mix, y que abarcan el Producto, el Precio, la Distribución y la Comunicación. Dentro de las herramientas destinadas al producto se encuentra la matriz BCG (Boston Consulting Group), que está orientada a gestión, sobre la base de la situación del pr...

  9. Composition and immunoreactivity of the A60 complex and other cell fractions from Mycobacterium bovis BCG.

    Science.gov (United States)

    Cocito, C; Vanlinden, F

    1995-02-01

    Surface static cultures of Mycobacterium bovis BCG contained cells embedded in an extracellular matrix, whose mechanical removal yielded free cells that were pressure disrupted and fractionated into cytoplasm and walls. Cell envelopes were either mechanically disrupted or extracted with detergents. Intracellular and extracellular fractions were analysed for proteins, polysaccharides, and antigen 6O (A60), a major complex immunodominant in tuberculosis. A60 was present in extracellular matrix, cytoplasm and walls: it represented a substantial portion of the proteins and polysaccharides of these fractions. While the protein/polysaccharide ratio varied according to the origin of A60 preparations, the electrophoretic patterns of A60 proteins (which accounted for the immunogenicity of the complex) remained unchanged. Western blots pointed to the proteins present within the 29-45 kDa range as the A60 components endowed with the highest immunogenicity level. Since the most heavily stained protein bands in SDS-PAGE patterns were located outside the region best recognized by antisera, a striking discordance was found between concentration and immunogenicity patterns of A60 proteins. The electrophoretic patterns of A60- and non-A60-proteins from cytoplasm were also different. A60 complexes in dot blots and some electrophoresed A60 proteins reacted with monoclonal antibodies directed against lipoarabinomannan (LAM), a highly immunogenic polymer of cell envelope. This contaminating compound was removed from A60 with organic solvents and detergents. SDS-PAGE and Western blot patterns of proteins from delipidated A60 were similar to those of native A60 proteins. PMID:7863264

  10. ISS Live!

    Science.gov (United States)

    Price, Jennifer; Harris, Philip; Hochstetler, Bruce; Guerra, Mark; Mendez, Israel; Healy, Matthew; Khan, Ahmed

    2013-01-01

    International Space Station Live! (ISSLive!) is a Web application that uses a proprietary commercial technology called Lightstreamer to push data across the Internet using the standard http port (port 80). ISSLive! uses the push technology to display real-time telemetry and mission timeline data from the space station in any common Web browser or Internet- enabled mobile device. ISSLive! is designed to fill a unique niche in the education and outreach areas by providing access to real-time space station data without a physical presence in the mission control center. The technology conforms to Internet standards, supports the throughput needed for real-time space station data, and is flexible enough to work on a large number of Internet-enabled devices. ISSLive! consists of two custom components: (1) a series of data adapters that resides server-side in the mission control center at Johnson Space Center, and (2) a set of public html that renders the data pushed from the data adapters. A third component, the Lightstreamer server, is commercially available from a third party and acts as an intermediary between custom components (1) and (2). Lightstreamer also provides proprietary software libraries that are required to use the custom components. At the time of this reporting, this is the first usage of Web-based, push streaming technology in the aerospace industry.

  11. Structural features of lipoarabinomannan from Mycobacterium bovis BCG. Determination of molecular mass by laser desorption mass spectrometry.

    Science.gov (United States)

    Venisse, A; Berjeaud, J M; Chaurand, P; Gilleron, M; Puzo, G

    1993-06-15

    It was recently shown that mycobacterial lipoarabinomannan (LAM) can be classified into two types (Chatterjee, D., Lowell, K., Rivoire B., McNeil M. R., and Brennan, P. J. (1992) J. Biol. Chem. 267, 6234-6239) according to the presence or absence of mannosyl residues (Manp) located at the nonreducing end of the oligoarabinosyl side chains. These two types of LAM were found in a pathogenic Mycobacterium tuberculosis strain and in an avirulent M. tuberculosis strain, respectively, suggesting that LAM with Manp characterizes virulent and "disease-inducing strains." We now report the structure of the LAM from Mycobacterium bovis Bacille Calmette-Guérin (BCG) strain Pasteur, largely used throughout the world as vaccine against tuberculosis. Using an up-to-date analytical approach, we found that the LAM of M. bovis BCG belongs to the class of LAMs capped with Manp. By means of two-dimensional homonuclear and heteronuclear scalar coupling NMR analysis and methylation data, the sugar spin system assignments were partially established, revealing that the LAM contained two types of terminal Manp and 2-O-linked Manp. From the following four-step process: (i) partial hydrolysis of deacylated LAM (dLAM), (ii) oligosaccharide derivatization with aminobenzoic ethyl ester, (iii) HPLC purification, (iv) FAB/MS-MS analysis; it was shown that the dimannosyl unit alpha-D-Manp-(1-->2)-alpha-D-Manp is the major residue capping the termini of the arabinan of the LAM. In this report, LAM molecular mass determination was established using matrix-assisted UV-laser desorption/ionization mass spectrometry which reveals that the LAM molecular mass is around 17.4 kDa. The similarity of the LAM structures between M. bovis BCG and M. tuberculosis H37Rv is discussed in regard to their function in the immunopathology of mycobacterial infection. PMID:8509380

  12. The Mean and Scatter of the Velocity Dispersion-Optical Richness Relation for MaxBCG Galaxy Clusters

    Energy Technology Data Exchange (ETDEWEB)

    Becker, M.R.; McKay, T.A.; /Michigan U.; Koester, B.; /Chicago U., Astron. Astrophys. Ctr.; Wechsler, R.H.; /KIPAC, Menlo Park /SLAC /Stanford U., Phys. Dept.; Rozo, E.; /Ohio State U.; Evrard, A.; /Michigan U. /Michigan U., MCTP; Johnston, D.; /Caltech, JPL; Sheldon, E.; /New York U.; Annis, J.; /Fermilab; Lau, E.; /Chicago U., Astron. Astrophys. Ctr.; Nichol, R.; /Portsmouth U., ICG; Miller, C.; /Michigan U.

    2007-06-05

    The distribution of galaxies in position and velocity around the centers of galaxy clusters encodes important information about cluster mass and structure. Using the maxBCG galaxy cluster catalog identified from imaging data obtained in the Sloan Digital Sky Survey, we study the BCG--galaxy velocity correlation function. By modeling its non-Gaussianity, we measure the mean and scatter in velocity dispersion at fixed richness. The mean velocity dispersion increases from 202 {+-} 10 km s{sup -1} for small groups to more than 854 {+-} 102 km s{sup -1} for large clusters. We show the scatter to be at most 40.5{+-}3.5%, declining to 14.9{+-}9.4% in the richest bins. We test our methods in the C4 cluster catalog, a spectroscopic cluster catalog produced from the Sloan Digital Sky Survey DR2 spectroscopic sample, and in mock galaxy catalogs constructed from N-body simulations. Our methods are robust, measuring the scatter to well within one-sigma of the true value, and the mean to within 10%, in the mock catalogs. By convolving the scatter in velocity dispersion at fixed richness with the observed richness space density function, we measure the velocity dispersion function of the maxBCG galaxy clusters. Although velocity dispersion and richness do not form a true mass--observable relation, the relationship between velocity dispersion and mass is theoretically well characterized and has low scatter. Thus our results provide a key link between theory and observations up to the velocity bias between dark matter and galaxies.

  13. Comparison of the effect of the viral paramunity-inducers BCG and levamisole on the growth of a radiation-induced transplanted osteosarcoma in mice

    International Nuclear Information System (INIS)

    Treatment with paramunity inducers Pind avi and Pind orf resulted in general in a smaller number of tumor takes as compared to BCG, Levamisol or untreated controls. Tumor growth curves were independent of treatment. Each experiment was replicated three times. A comparison of pooled results showed significant differences between Pind avi treatment and untreated controls for each level of tumor cells. When pooling levels of tumor cells and testing each replication separately there was a highly significant difference between Pind avi and controls and Pind orf and controls. BCG and Levamisole showed no significant difference to controls. Pind avi and Pind orf considerably raised the number of tumor cells needed to results in 50% takes. For BCG on the other hand less cells were needed. The TD50 with Levamisole was somewhat higher than the TD50 of controls. The formation of metastases was infrequent (0,65%), and only seen in lung tissue. (orig./MG)

  14. Comparison of BCG, MPL and cationic liposome adjuvant systems in leishmanial antigen vaccine formulations against murine visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Bhowmick Sudipta

    2010-06-01

    Full Text Available Abstract Background The development of an effective vaccine against visceral leishmaniasis (VL caused by Leishmania donovani is an essential aim for controlling the disease. Use of the right adjuvant is of fundamental importance in vaccine formulations for generation of effective cell-mediated immune response. Earlier we reported the protective efficacy of cationic liposome-associated L. donovani promastigote antigens (LAg against experimental VL. The aim of the present study was to compare the effectiveness of two very promising adjuvants, Bacille Calmette-Guerin (BCG and Monophosphoryl lipid A (MPL plus trehalose dicorynomycolate (TDM with cationic liposomes, in combination with LAg, to confer protection against murine VL. Results All the three formulations afforded significant protection against L. donovani in both the visceral organs, liver and spleen. Although comparable level of protection was observed in BCG+LAg and MPL-TDM+LAg immunized mice, highest level of protection was exhibited by the liposomal LAg immunized group. Significant increase in anti-LAg IgG levels were detected in both MPL-TDM+LAg and liposomal LAg immunized animals with higher levels of IgG2a than IgG1. But BCG+LAg failed to induce any antibody response. As an index of cell-mediated immunity DTH responses were measured and significant response was observed in mice vaccinated with all the three different formulations. However, highest responses were observed with liposomal vaccine immunization. Comparative evaluation of IFN-γ and IL-4 responses in immunized mice revealed that MPL-TDM+LAg group produced the highest level of IFN-γ but lowest IL-4 level, while BCG+LAg demonstrated generation of suboptimum levels of both IFN-γ and IL-4 response. Elicitation of moderate levels of prechallenge IFN-γ along with optimum IL-4 corresponds with successful vaccination with liposomal LAg. Conclusion This comparative study reveals greater effectiveness of the liposomal vaccine for

  15. The XXL survey XV: Evidence for dry merger driven BCG growth in XXL-100-GC X-ray clusters

    OpenAIRE

    Lavoie, S.; Willis, J. P.; Democles, J.; Eckert, D; F. Gastaldello; Smith, G. P.; Lidman, C.; Adami, C.; Pacaud, F.; Pierre, M.; Clerc, N.; Giles, P.; Lieu, M.; Chiappetti, L.; Altieri, B.

    2016-01-01

    The growth of brightest cluster galaxies is closely related to the properties of their host cluster. We present evidence for dry mergers as the dominant source of BCG mass growth at $z\\lesssim1$ in the XXL 100 brightest cluster sample. We use the global red sequence, H$\\alpha$ emission and mean star formation history to show that BCGs in the sample possess star formation levels comparable to field ellipticals of similar stellar mass and redshift. XXL 100 brightest clusters are less massive on...

  16. The results of treatments and complications of immunotherapy (BCG and alpha-interferon in superficial TCC of bladder

    Directory of Open Access Journals (Sweden)

    Jabalameli P

    1994-04-01

    Full Text Available The treatment of choice for bladder tumors is TUR, but because of high incidence of recurrence in these tumors, various treatments are suggested. In one study, 32 patients involved with superficial T.C.C. of bladder selected and divided in two equal groups. In the first group, after T.U.R, 10 million IU of a alpha-interferon was injected into the bladder through a catheter and in the other group, after TUR, they treated with injection of BCG into bladders. The results of these two drugs in prevention of recurrence and their side effects were studied and compaired

  17. Live Virus Smallpox Vaccine

    Science.gov (United States)

    ... A - Z Index SMALLPOX FACT SHEET The Live Virus Smallpox Vaccine The vaccinia virus is the "live ... it cannot cause smallpox. What is a "live virus" vaccine? A "live virus" vaccine is a vaccine ...

  18. Dynamic observation of immune responses induced in mice by immunization with a recombinant BCG-TSOL18 vaccine of Taenia solium%猪带绦虫重组BCG-TSOL18疫苗诱导小鼠免疫应答的动态观察

    Institute of Scientific and Technical Information of China (English)

    杨凤娇; 江楠; 周泠; 刘晖; 王灵军; 周必英

    2015-01-01

    Objective To dynamically observe humoral and cellular immune responses induced in mice by immunization with a recombinant BCG-TSOL18 vaccine of Taenia solium.Methods Totally 80 Kunming mice were divided into 4 groups by using random number table according to body mass, 20 mice in each group: rBCG-TSOL18 intraperitoneal injection group [mice were vaccinated with 5 × 106 colony forming units (CFU) recombinant BCG-TSOL18 vaccine of Taenia solium through intraperitoneal injection], rBCG-TSOL18 intragastric administration group(mice were vaccinated with 4 × 108 CFU recombinant BCG-TSOL18 vaccine of Taenia solium through intragastric administration), BCG control (mice were vaccinated with 5 × 106 CFU BCG through intraperitoneal injection), PBS control (mice were vaccinated with PBS through intraperitoneal injection).Zero, 2, 4, 6 and 8 weeks after immunization, eye blood was collected and serum w as separated.Levels of specific IgG and IgG2a were detected by enzyme linked immunosorbent assay (ELISA).Proliferation level of spleen lymphocytes was detected by CCK-8.Levels of interleukin-2 (IL-2) and IL-4 were determined by ELISA.Results The level of specific IgG in rBCG-TSOL18 intraperitoneal injection group and rBCG-TSOL18 intragastric administration group increased from 2 to 8 weeks, and reached the highest level by the 6th week (0.310 ± 0.022, 0.356 ± 0.026).Compared with 0 week in the same group, BCG and PBS control group of the same time periods (0.054 ± 0.005, 0.057 ± 0.006, 0.093 ± 0.014, 0.085 ± 0.010), there were statistically significant differences (all P < 0.05).The level of specific IgG2a increased from 2 to 8 weeks, and reached the highest level by the 6th week (0.965 ± 0.031, 1.144 ± 0.049).Compared with 0 week in the same group, BCG and PBS control group of the same time periods (0.102 ± 0.014, 0.093 ± 0.012, 0.115 ± 0.012, 0.103 ± 0.013), there were statistically significant differences (all P < 0.05).The proliferation level of spleen

  19. Oral re-vaccination of Eurasian wild boar with Mycobacterium bovis BCG yields a strong protective response against challenge with a field strain

    OpenAIRE

    Gortázar, Christian; Beltrán-Beck, Beatriz; Joseba M. Garrido; Aranaz, Alicia; Sevilla, Iker A.; Boadella, Mariana; Lyashchenko, Konstantin P; Galindo, Ruth C.; Montoro, Vidal; Domínguez, Lucas; Juste, Ramón; De La Fuente, Jose

    2014-01-01

    Abstract Background Field vaccination trials with Mycobacterium bovis BCG, an attenuated mutant of M. bovis, are ongoing in Spain, where the Eurasian wild boar (Sus scrofa) is regarded as the main driver of animal tuberculosis (TB). The oral baiting strategy consists in deploying vaccine baits twice each summer, in order to gain access to a high proportion of wild boar piglets. The aim of this study was to assess the response of wild boar to re-vaccination with BCG and to subsequent challenge...

  20. Living Nanomachines

    Science.gov (United States)

    Carlier, M.-F.; Helfer, E.; Wade, R.; Haraux, F.

    The living cell is a kind of factory on the microscopic scale, in which an assembly of modular machines carries out, in a spatially and temporally coordinated way, a whole range of activities internal to the cell, including the synthesis of substances essential to its survival, intracellular traffic, waste disposal, and cell division, but also activities related to intercellular communication and exchanges with the outside world, i.e., the ability of the cell to change shape, to move within a tissue, or to organise its own defence against attack by pathogens, injury, and so on. These nanomachines are made up of macromolecular assemblies with varying degrees of complexity, forged by evolution, within which work is done as a result of changes in interactions between proteins, or between proteins and nucleic acids, or between proteins and membrane components. All these cell components measure a few nanometers across, so the mechanical activity of these nanomachines all happens on the nanometric scale. The directional nature of the work carried out by biological nanomachines is associated with a dissipation of energy. As examples of protein assemblies, one could mention the proteasome, which is responsible for the degradation of proteins, and linear molecular motors such as actomyosin, responsible for muscle contraction, the dynein-microtubule system, responsible for flagellar motility, and the kinesin-microtubule system, responsible for transport of vesicles, which transform chemical energy into motion. Nucleic acid-protein assemblies include the ribosome, responsible for synthesising proteins, polymerases, helicases, elongation factors, and the machinery of DNA replication and repair; the mitotic spindle is an integrated system involving several of these activities which drive chromosome segregation. The machinery coupling membranes and proteins includes systems involved in the energy metabolism, such as the ATP synthase rotary motor, signalling cascades, endocytosis

  1. Strategic analysis of PKM Duda SA. on Polish meat market with the application of BCG growth-share matrix

    Directory of Open Access Journals (Sweden)

    Anna Zielińska-Chmielewska

    2012-01-01

    Full Text Available The main goal of this paper was to examine the market position of one leading meat processing enterprise PKM Duda SA. on the domestic meat market. The assessment of the activity portfolio on its three strategic units was undertaken with the usage of BCG matrix. The PKM Duda SA. was chosen for the study because: a processes more than 20 tons of slaughter per week, b is located in the country of origin, c exists on Warsaw Stock Exchange Market, d preserves continuity of its database in Monitor Polski „B”. The analysis proved that all three examined strategic units have different market shares and operate on markets of a different acceleration. The highest income rate brings the meat processing unit (B, the lowest slaughter unit (A. The market position of PKM Duda SA. can be improved when a retail trade unit (B moves away from question marks into stars. Although BCG matrix draws a fast and a complex strategic situation, is not free from disadvantages. That is the reason why further, also portfolio, analysis should be im-plemented.

  2. The XXL survey XV: Evidence for dry merger driven BCG growth in XXL-100-GC X-ray clusters

    CERN Document Server

    Lavoie, S; Democles, J; Eckert, D; Gastaldello, F; Smith, G P; Lidman, C; Adami, C; Pacaud, F; Pierre, M; Clerc, N; Giles, P; Lieu, M; Chiappetti, L; Altieri, B; Ardila, F; Baldry, I; Bongiorno, A; Desai, S; Elyiv, A; Faccioli, L; Gardner, B; Garilli, B; Groote, M W; Guennou, L; Guzzo, L; Hopkins, A M; Liske, J; McGee, S; Melnyk, O; Owers, M S; Poggianti, B; Ponman, T J; Scodeggio, M; Spitler, L; Tuffs, R J

    2016-01-01

    The growth of brightest cluster galaxies is closely related to the properties of their host cluster. We present evidence for dry mergers as the dominant source of BCG mass growth at $z\\lesssim1$ in the XXL 100 brightest cluster sample. We use the global red sequence, H$\\alpha$ emission and mean star formation history to show that BCGs in the sample possess star formation levels comparable to field ellipticals of similar stellar mass and redshift. XXL 100 brightest clusters are less massive on average than those in other X-ray selected samples such as LoCuSS or HIFLUGCS. Few clusters in the sample display high central gas concentration, rendering inefficient the growth of BCGs via star formation resulting from the accretion of cool gas. Using measures of the relaxation state of their host clusters, we show that BCGs grow as relaxation proceeds. We find that the BCG stellar mass corresponds to a relatively constant fraction 1\\%\\ of the total cluster mass in relaxed systems. We also show that, following a cluste...

  3. Successive Intramuscular Boosting with IFN-Alpha Protects Mycobacterium bovis BCG-Vaccinated Mice against M. lepraemurium Infection

    Directory of Open Access Journals (Sweden)

    G. G. Guerrero

    2015-01-01

    Full Text Available Leprosy caused by Mycobacterium leprae primarily affects the skin and peripheral nerves. As a human infectious disease, it is still a significant health and economic burden on developing countries. Although multidrug therapy is reducing the number of active cases to approximately 0.5 million, the number of cases per year is not declining. Therefore, alternative host-directed strategies should be addressed to improve treatment efficacy and outcome. In this work, using murine leprosy as a model, a very similar granulomatous skin lesion to human leprosy, we have found that successive IFN-alpha boosting protects BCG-vaccinated mice against M. lepraemurium infection. No difference in the seric isotype and all IgG subclasses measured, neither in the TH1 nor in the TH2 type cytokine production, was seen. However, an enhanced iNOS/NO production in BCG-vaccinated/i.m. IFN-alpha boosted mice was observed. The data provided in this study suggest a promising use for IFN-alpha boosting as a new prophylactic alternative to be explored in human leprosy by targeting host innate cell response.

  4. Construction and expression of a recombinant BCG-TSOL18 vaccine of Taenia solium%猪带绦虫重组 BCG-TSOL18疫苗构建及其表达

    Institute of Scientific and Technical Information of China (English)

    杨凤娇; 周必英

    2015-01-01

    We constructed a recombinant Bacillus Calmette‐Guerin(BCG)‐TSOL18 vaccine of Taenia solium and observed the expression of the TSOL18 gene in BCG .The TSOL18 gene of Taenia solium was obtained from the recombinant plasmid pGEX‐TSOL18 by digestion method and cloned into Escherichia coli (E .coli)‐mycobacterium shuttle plasmid pMV261 to con‐struct the recombinant plasmid pMV261‐TSOL18 of Taenia solium ,and the recombinant plasmid was identified by restriction enzyme digestion ,PCR and DNA sequencing .Then ,the recombinant plasmid was transformed into BCG by electroporation to construct the recombinant BCG‐TSOL18 vaccine of Taenia solium ,and the vaccine was identified by PCR .The expression of the TSOL18 gene in BCG was identified by SDS‐PAGE and Western blot .The 393 bp TSOL18 gene fragment was successfully obtained by restriction enzyme digestion .Restriction enzyme digestion ,PCR and DNA sequencing suggested that the recombi‐nant plasmid pMV261‐TSOL18 of Taenia solium was successfully constructed .PCR confirmed that the recombinant plasmid pMV261‐TSOL18 of Taenia solium was successfully transformed into BCG ,suggesting that the recombinant BCG‐TSOL18 vaccine of Taenia solium was successfully constructed .SDS‐PAGE showed that the relative molecular mass (Mr) of TSOL18 target protein was approximately 14 .7 kD .Results of western blot showed the TSOL18 target protein could be recognized by rabbit antiserum or cysticercosis swine serum .The recombinant BCG‐TSOL18 vaccine of Taenia solium was successfully con‐structed .The TSOL18 gene of Taeniasolium was successfully expressed in BCG and the expressed TSOL18 recombinant pro‐tein had specific antigenicity .This result would lay a foundation for further study of the vaccine .%目的:构建猪带绦虫重组BCG‐TSOL18疫苗,研究TSOL18基因在BCG中的表达情况。方法通过酶切的方法从重组质粒pGEX‐TSOL18获取猪带绦虫TSOL18基因,将其定向克隆到大肠

  5. Enhanced effect of BCG vaccine against pulmonary Mycobacterium tuberculosis infection in mice with lung Th17 response to mycobacterial heparin-binding hemagglutinin adhesin antigen.

    Science.gov (United States)

    Fukui, Masayuki; Shinjo, Kikuko; Umemura, Masayuki; Shigeno, Satoko; Harakuni, Tetsuya; Arakawa, Takeshi; Matsuzaki, Goro

    2015-12-01

    Although the BCG vaccine can prevent tuberculosis (TB) in infants, its ability to prevent adult pulmonary TB is reportedly limited. Therefore, development of a novel effective vaccine against pulmonary TB has become an international research priority. We have previously reported that intranasal vaccination of mice with a mycobacterial heparin-binding hemagglutinin adhesin (HBHA) plus mucosal adjuvant cholera toxin (CT) enhances production of IFN-γ and anti-HBHA antibody and suppresses extrapulmonary bacterial dissemination after intranasal infection with BCG. In the present study, the effects of intranasal HBHA + CT vaccine on murine pulmonary Mycobacterium tuberculosis (Mtb) infection were examined. Intranasal HBHA + CT vaccination alone failed to reduce the bacterial burden in the infected lung. However, a combination vaccine consisting of s.c. BCG priming and an intranasal HBHA + CT booster significantly enhanced protective immunity against pulmonary Mtb infection on day 14 compared with BCG vaccine alone. Further, it was found that intranasal HBHA + CT vaccine enhanced not only IFN-γ but also IL-17A production by HBHA-specific T cells in the lung after pulmonary Mtb infection. Therefore, this combination vaccine may be a good candidate for a new vaccine strategy against pulmonary TB. PMID:26577130

  6. The lack of therapeutic effects in mice of the combined gamma-irradiated Mycobacterium leprae and viable BCG against Mycobacterium leprae infection

    International Nuclear Information System (INIS)

    Gamma-irradiated M. leprae in combination with BCG given once biweekly to mice from 2 weeks for up to 187 days after infection with M. leprae caused no significant growth inhibition of M. leprae, at the site of the infection. (author)

  7. Effect of 50 000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial

    DEFF Research Database (Denmark)

    Diness, B.R.; Roth, A.; Nante, E.; Fisker, A.B.; Lisse, I.M.; Yazdanbakhsh, M.; Whittle, H.; Rodrigues, A.; Aaby, P.; Benn, Christine Stabell

    2008-01-01

    .84 (0.55 to 1.27) compared with 1.39 (0.90 to 2.14) in girls (P for interaction=0.10). An explorative analysis revealed a strong interaction between vitamin A and season of administration. Conclusions Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African...

  8. Graft-versus-host reaction-like phenomenon induced by BCG in mice lethally irradiated and transferred with syngeneic bone marrow cells

    International Nuclear Information System (INIS)

    Heat-killed BCG in paraffin exerted a lethal effect on C57BL/6 mice irradiated lethally and transferred with syngeneic bone marrow cells. Such an effect was not detectable when mice were subjected to adult thymectomy and used as the hosts. Lymphoid cells from such nonthymectomized mice exhibited cytotoxicity to syngeneic tumor cells but not to allogeneic tumor cells in an in vivo cytotoxicity test and induced splenomegaly in sublethally irradiated syngeneic recipients after systemic transfer. The cytotoxicity of such lymphoid cells was abolished by a treatment with anti-theta serum and complement. In the bone marrow of mice irradiated and transferred with bone marrow cells, the number of nucleated cells, the ratio of mycloid to erythroid cell series, and the percentage of lymphocytes were increased by BCG injection. These results suggest the possibility that self-tolerance may be broken by BCG injection. These results suggest the possibility that self-tolerance may be broken by BCG stimulation in the process of reconstitution of lymphoid cells in the irradiated mice

  9. Fecal volatile organic compound profiles from white-tailed deer (Odocoileus virginianus) as indicators of Mycobacterium bovis exposure or Mycobacterium bovis bacille Calmette-Guerin (BCG) vaccination

    Science.gov (United States)

    White-tailed deer (Odocoileus virginianus) serve as a reservoir for bovine tuberculosis, caused by Mycobacterium bovis, and can be a source of infection in cattle. Vaccination with M. bovis bacille Calmette-Guerin (BCG) is being considered for management of bovine tuberculosis in deer. Presently, no...

  10. Human beta casein fragment (54-59 modulates M. bovis BCG survival and basic transcription factor 3 (BTF3 expression in THP-1 cell line.

    Directory of Open Access Journals (Sweden)

    Dharamsheela Thakur

    Full Text Available Immunostimulatory peptides potentiate the immune system of the host and are being used as a viable adjunct to established therapeutic modalities in treatment of cancer and microbial infections. Several peptides derived from milk protein have been reported to induce immunostimulatory activity. Human β -casein fragment (54-59, natural sequence peptide (NS carrying the Val-Glu-Pro-Ile-Pro-Tyr amino acid residues, was reported to activate the macrophages and impart potent immunostimulatory activity. In present study, we found that this peptide increases the clearance of M. bovis BCG from THP-1 cell line in vitro. The key biomolecules, involved in the clearance of BCG from macrophage like, nitric oxide, pro-inflammatory cytokines and chemokines, were not found to be significantly altered after peptide treatment in comparison to the untreated control. Using proteomic approach we found that BTF3a, an isoform of the Basic Transcription Factor, BTF3, was down regulated in THP-1 cell line after peptide treatment. This was reconfirmed by real time RT-PCR and western blotting. We report the BTF3a as a novel target of this hexapeptide. Based on the earlier findings and the results from the present studies, we suggest that the down regulation of BTF3a following the peptide treatment may augment the M. bovis BCG mediated apoptosis resulting in enhanced clearance of M. bovis BCG from THP-1 cell line.

  11. A Mycobacterium bovis BCG-naked DNA prime-boost vaccination strategy induced CD4⁺ and CD8⁺ T-cell response against Mycobacterium tuberculosis immunogens.

    Science.gov (United States)

    Lu, Miao; Xia, Zhi Yang; Bao, Lang

    2014-01-01

    Mycobacterium tuberculosis infection is still a major global public health problem. Presently the only tuberculosis (TB) vaccine available is Bacille Calmette-Guérin (BCG), although it fails to adequately protect against pulmonary TB in adults. To solve this problem, the development of a new effective vaccine is urgently desired. BCG-prime DNA-booster vaccinations strategy has been shown to induce greater protection against tuberculosis (TB) than BCG alone. Some studies have demonstrated that the two genes (Rv1769 and Rv1772) are excellent T-cell antigens and could induce T-cell immune responses. In this research, we built BCG-C or BCG-P prime-recombination plasmid PcDNA3.1-Rv1769 or PcDNA3.1-Rv1772 boost vaccinations strategy to immunize BALB/c mice and evaluated its immunogenicity. The data suggests that the BCG-C+3.1-72 strategy could elicit the most long-lasting and strongest Th1-type cellular immune responses and the BCG-C+3.1-69 strategy could induce the high level CD8+ T-cell response at certain time points. These findings support the ideas that the prime-boost strategy as a combination of vaccines may be better than a single vaccine for protection against tuberculosis. PMID:24741595

  12. Comparative Study on the Immunogenicity between Recombinant MS-Sj26GST Vaccine and Recombinant BCG-Sj26GST Vaccine in Schistosoma japonicum

    Institute of Scientific and Technical Information of China (English)

    戴五星; 高红; 黄海浪; 袁野; 胡佳杰; 皇甫永穆

    2003-01-01

    The BALB/c mice were immunized with rMS-Sj26GST and rBCG-Sj26GST vaccine inSchistosoma japonicum by subcutaneous injection. After they were immunized for 8 weeks, the eye-balls were removed to get blood and macrophages of abdominal cavity and spleen cells were harves-ted. The lymphocytic stimulating index (SI) was used to measure the cellular proliferating abilityand NO release was used to measure the phagocytic activity of the macrophages. By using ELISAkit, the levels of interleukin-2 (IL-2) and interferon-γ(IFN-γ) in serum and the splenic lymphocyt-ic cultured supernatant were detected. The results showed that after the mice were immunized with106 CFU of rMS-Sj26GST and rBCG-Sj26GST vaccine separately by subcutaneous injection, prolif-erating ability of splenic lymphocytes in the mice showed no difference (P>0.05), but both weresignificantly increased as compared with that in the control group(P<0.05); The contents of NOin the intraperitoneal macrophages of rMS-Sj26GST vaccine group were significantly lower than inthe control group (P<0. 001) and rBCG-Sj26GST vaccine group (P<0. 01); The levels of serumIL-2 in the rMS-Sj26GST vaccine group were significantly increased as compared with that in thecontrol group (P<0. 001), vector group (P<0.01) and rBCG-Sj26GST vaccine group (P<0.05);The contents of serum IFN-γ in the rMS-Sj26GST vaccine group were significantly increased ascompared with that in the control group (P<0.01) and rBCG-Sj26GST vaccine group (P<0.05).The contents of IFN-γ in the cultured supernatant were significantly lower than those of rBCG-Sj26GST vaccine group (P<0. 001), but were significantly increased as compared with that in thecontrol group (P<0.01). It was indicated that both vaccines could enhance the immune response ofthe mice, but rMS-Sj26GST vaccine had stronger immunogenicity than rBCG-Sj26GST vaccine.

  13. Living Gluten Free

    Science.gov (United States)

    ... please turn JavaScript on. Feature: Celiac Disease Living Gluten Free Past Issues / Spring 2015 Table of Contents ... Learning to Live Well with Celiac Disease / Living Gluten-Free Spring 2015 Issue: Volume 10 Number 1 ...

  14. Comparative Ser/Thr/Tyr phosphoproteomics between two mycobacterial species: the fast growing Mycobacterium smegmatis and the slow growing Mycobacterium bovis BCG.

    Science.gov (United States)

    Nakedi, Kehilwe C; Nel, Andrew J M; Garnett, Shaun; Blackburn, Jonathan M; Soares, Nelson C

    2015-01-01

    Ser/Thr/Tyr protein phosphorylation plays a critical role in regulating mycobacterial growth and development. Understanding the mechanistic link between protein phosphorylation signaling network and mycobacterial growth rate requires a global view of the phosphorylation events taking place at a given time under defined conditions. In the present study we employed a phosphopeptide enrichment and high throughput mass spectrometry-based strategy to investigate and qualitatively compare the phosphoproteome of two mycobacterial model organisms: the fast growing Mycobacterium smegmatis and the slow growing Mycobacterium bovis BCG. Cells were harvested during exponential phase and our analysis detected a total of 185 phospho-sites in M. smegmatis, of which 106 were confidently localized [localization probability (LP) = 0.75; PEP = 0.01]. By contrast, in M. bovis BCG the phosphoproteome comprised 442 phospho-sites, of which 289 were confidently localized. The percentage distribution of Ser/Thr/Tyr phosphorylation was 39.47, 57.02, and 3.51% for M. smegmatis and 35, 61.6, and 3.1% for M. bovis BCG. Moreover, our study identified a number of conserved Ser/Thr phosphorylated sites and conserved Tyr phosphorylated sites across different mycobacterial species. Overall a qualitative comparison of the fast and slow growing mycobacteria suggests that the phosphoproteome of M. smegmatis is a simpler version of that of M. bovis BCG. In particular, M. bovis BCG exponential cells exhibited a much more complex and sophisticated protein phosphorylation network regulating important cellular cycle events such as cell wall biosynthesis, elongation, cell division including immediately response to stress. The differences in the two phosphoproteomes are discussed in light of different mycobacterial growth rates. PMID:25904896

  15. Comparative Ser/Thr/Tyr phosphoproteomics between two Mycobacterial species: The fast growing Mycobacterium smegmatis and the slow growing Mycobacterium bovis BCG.

    Directory of Open Access Journals (Sweden)

    Kehilwe Confidence Nakedi

    2015-04-01

    Full Text Available Ser/Thr/Tyr protein phosphorylation plays a critical role in regulating mycobacterial growth and development. Understanding the mechanistic link between protein phosphorylation signaling network and mycobacterial growth rate requires a global view of the phosphorylation events taking place at a given time under defined conditions. In the present study we employed a phosphopeptide enrichment and high throughput mass spectrometry-based strategy to investigate and qualitatively compare the phosphoproteome of two mycobacterial model organisms: the fast growing Mycobacterium smegmatis and the slow growing Mycobacterium bovis BCG. Cells were harvested during exponential phase and our analysis detected a total of 185 phospho-sites in M. smegmatis, of which 106 were confidently localized (localization probability (LP =0.75; PEP=0.01. By contrast, in M. bovis BCG the phosphoproteome comprised 442 phospho-sites, of which 289 were confidently localized. The percentage distribution of Ser/Thr/Tyr phosphorylation was 39.47, 57.02 and 3.51 % for M. smegmatis and 35, 61.6 and 3.1% for M. bovis BCG. Moreover, our study identified a number of conserved Ser/Thr phosphorylated sites and conserved Tyr phosphorylated sites across different mycobacterial species. Overall a qualitative comparison of the fast and slow growing mycobacteria suggests that the phosphoproteome of M. smegmatis is a simpler version of that of M. bovis BCG. In particular, M. bovis BCG exponential cells exhibited a much more complex and sophisticated protein phosphorylation network regulating important cellular cycle events such as cell wall biosynthesis, elongation, cell division including immediately response to stress. The differences in the two phosphoproteomes are discussed in light of different mycobacterial growth rates.

  16. Lack of a Negative Effect of BCG-Vaccination on Child Psychomotor Development: Results from the Danish Calmette Study - A Randomised Clinical Trial

    Science.gov (United States)

    Kjærgaard, Jesper; Stensballe, Lone Graff; Birk, Nina Marie; Nissen, Thomas Nørrelykke; Foss, Kim Thestrup; Thøstesen, Lisbeth Marianne; Pihl, Gitte Thybo; Andersen, Andreas; Kofoed, Poul-Erik; Pryds, Ole; Greisen, Gorm

    2016-01-01

    Objectives To assess the non-specific effect of Bacillus Calmette-Guérin (BCG) vaccination at birth on psychomotor development. Design This is a pre-specified secondary outcome from a randomised, clinical trial. Setting Maternity units and paediatric wards at three university hospitals in Denmark. Participants Children born at gestational age (GA) 32 weeks and above. All women planning to give birth at the three sites were invited during the recruitment period. Out of 4262 randomised children, 144 were premature (GA BCG and 2133 randomised (73 premature) to the control group. Interventions BCG vaccination 0.05 ml was given intradermally in the upper left arm at the hospital within seven days of birth. Children in the control group did not receive any intervention. Parents were not blinded to allocation. Main outcome measures Psychomotor development measured using Ages and Stages Questionnaire (ASQ) completed by the parents at 12 months. Additionally, parents of premature children (gestational age BCG vs. control, 95% confidence interval; -3.7 to 2.4), p = 0.67, corresponding to an effect size of Cohen’s d = -0.015 (-0.082 to 0.052). The mean difference in ASQ score for premature children at 22 months was -7.8 points (-20.6 to 5.0, p = 0.23), d = -0.23 (-0.62 to 0.15). Conclusions A negative non-specific effect of BCG vaccination at birth on psychomotor development was excluded in term children. Trial Registration ClinicalTrials.gov NCT01694108 PMID:27123570

  17. Selection bias: neighbourhood controls and controls selected from those presenting to a Health Unit in a case control study of efficacy of BCG revaccination

    Directory of Open Access Journals (Sweden)

    de Souza Wayner V

    2007-02-01

    Full Text Available Abstract Background In most case control studies the hardest decision is the choice of the control group, as in the ideal control group the proportion exposed is the same as in the population that produced the cases. Methods A comparison of two control groups in a case control study of the efficacy of BCG revaccination. One group was selected from subjects presenting to the heath unit the case attended for routine prevention and care; the second group was selected from the neighbourhood of cases. All Health Units from which controls were selected offered BCG revaccination. Efficacy estimated in a randomized control trial of BCG revaccination was used to establish that the neighbourhood control group was the one that gave unbiased results. Results The proportion of controls with scars indicating BCG revaccination was higher among the control group selected from Health Unit attenders than among neighbourhood controls. This excess was not removed after control for social variables and history of exposure to tuberculosis, and appears to have resulted from the fact that people attending the Health Unit were more likely to have been revaccinated than neighbourhood controls, although we can not exclude an effect of other unmeasured variables. Conclusion In this study, controls selected from people presenting to a Health Unit overrepresented exposure to BCG revaccination. Had the results from the HU attenders control group been accepted this would have resulted in overestimation of vaccine efficacy. When the exposure of interest is offered in a health facility, selection of controls from attenders at the facility may result in over representation of exposure in controls and selection bias.

  18. Infección diseminada por BCG en la Región de Los Lagos, Chile: Reporte de cinco casos clínicos Disseminated infection by BCG in Región de Los Lagos, Chile: Five cases report

    Directory of Open Access Journals (Sweden)

    ALEXIS STRICKLER P

    2009-01-01

    Full Text Available El bacilo Calmette-Guérin (BCG, es la cepa atenuada de Mycobacterium bovis utilizada en países en vías de desarrollo para la prevención de formas graves de tuberculosis. La vacuna BCG neonatal se administra en países con alta prevalencia de la enfermedad. La mayoría de los vacunados no presenta reacciones adversas, algunos evidencian reacciones secundarias a una inmunidad alterada del huésped. Dichas reacciones varían desde una simple adenomegalia ipsilateral a la inoculación de BCG, hasta una infección diseminada, a menudo mortal. La infección diseminada se ha descrito en pacientes inmuno deficientes secundarios, primarios y en pacientes con defectos genéticos del eje interleuquina 12-23 (IL12/23-interferón gama (IFN-γ denominados "Síndrome de predisposición mendeliana a infecciones micobacterianas" (PMIM. Describimos cinco pacientes con infección por M. bovis-BCG diagnosticados entre 1995-2008, en el Hospital Base de Puerto Montt, Región de Los Lagos, Chile que cumplen con los criterios del PMIM.The bacillus Calmette-Guérin (BCG is the attenuated strain of Mycobacterium bovis used in developing countries for preventing serious forms of tuberculosis. The neonatal BCG vaccine is applied in countries with high prevalence of tuberculosis. Most of the vaccinated individuáis develop no adverse reactions; although, some subjects show side effects due to a host altered immunity. These reactions range from a simple adenomegaly in the same side of BCG vaccine inoculation, to a spread infection, often fatal. A regional or systemic spread has been described in patients with secondary or primary immunodeficiencies and partial or total genetic defects of interleukin IL-12/23 and IFN-γ called as a whole "Mendelian susceptibility to mycobacterial infections" (MSMD. We describe five patients infected with M. bovis BCG-diagnosed between 1995-2008, at the base hospital in the city of Puerto Montt, Región de Los Lagos, Chile. These patients

  19. Immune systems in developed and developing countries; implications for the design of vaccines that will work where BCG does not.

    Science.gov (United States)

    Rook, Graham A W; Dheda, Keertan; Zumla, Alimuddin

    2006-01-01

    New vaccine candidates for tuberculosis are beginning to enter clinical trials. In this review we discuss issues surrounding the design of these candidates, and the way they were screened in animal models. First, screening vaccines for their ability to attenuate inevitably fatal tuberculosis in immunologically naïve mice might be leading to the selection of inappropriate candidates. We need to screen vaccines for their ability to stop the development of progressive disease, since this is what they must achieve in man. A solution to this problem is proposed. Secondly, we point out that some mouse models of tuberculosis in laboratories in developing countries, where exposure to environmental mycobacteria is large, mimic neglected aspects of human disease more closely than do low-dose infections in hyper-susceptible immunologically naïve mice in the USA or Europe. We need to think more about geographical differences in immunological experience, and these mouse models can help us. Thirdly, we conclude that in developing countries where BCG fails this is not because there is too little Th1 response, but rather because the Th1 response is rendered ineffective and immunopathological by other subversive mechanisms, including IL-4 responses and inappropriate regulatory T cell function. Therefore, we suggest that vaccines that will work in those countries might need to have immunoregulatory properties that can switch off pre-existing subversive mechanisms, and block their development in the future. The development of such vaccines, that might work where BCG does not, will require a greater understanding of the roles of the many types of regulatory T cell in tuberculosis. PMID:16510309

  20. [Commemorative lecture of receiving Imamura Memorial Prize. II. Mode of action of oligonucleotide fraction extracted from Mycobacterium bovis BCG].

    Science.gov (United States)

    Yamamoto, S

    1994-09-01

    A fraction extracted from Mycobacterium bovis BCG was found to exhibit strong antitumor activity. This fraction, which was designated MY-1, caused some animal tumors to regress and/or prevent metastasis very effectively. MY-1 after digestion with DNase had almost completely reduced activity, while MY-1 digested with RNase did not. MY-1 also augmented natural killer (NK) cell activity of mouse spleen cells in vitro, and produced factors which showed anti-viral activity and rendered macrophages cytotoxic towards tumor cells. The function of the factor to activate macrophages was destroyed by treatment with anti-interferon (IFN)-gamma antibody, while the anti-viral activity was destroyed by treatment with anti-INF alpha/beta antibody. The oligonucleotides contained in MY-1 distributed in a broad range of molecular size, and peaked at 45 nucleotides. We synthesized 13 kinds of 45-mer nucleotides with sequence present in the known cDNA encoding various BCG proteins. Six out of these oligonucleotides, which contained one or more hexameric palindromic structures, showed strong antitumor activity, while the other without palindrome did not. These active oligonucleotides possessed the capability to induce IFN and to augment NK cell activity of mouse spleen cells by coincubation in vitro. When a portion of the sequence of the inactive oligonucleotides was substituted with either palindromic sequence of GACGTC, AGCGCT or AACGTT, the oligonucleotide acquired the ability to augment NK activity. In contrast, the oligonucleotides substituted with another palindromic sequence such as ACCGGT was without effect. Furthermore, exchange of two neighboring mononucleotides within, but not outside, the active palindromic sequence destroyed the ability of the oligonucleotide to augment NK activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7526022

  1. Cell-mediated immunity in operable bronchial carcinoma: the effect of injecting irradiated autologous tumour cells and BCG

    International Nuclear Information System (INIS)

    In 52 patients undergoing tests of cell-mediated immunity before surgical resection of bronchial carcinoma a positive tuberculin test result was found in 71% compared with 68% of age - and sex-matched controls. Sensitization to DNCB occurred in 52% of 37 patients but in 78% controls. There was depression of lymphocyte transformation by PPD in 19 patients compared with controls (p=0.001), but there was no difference in lymphocyte transformation by PHA pr pokeweed mitogen between 34 patients and controls. In a pilot study patients were randomly allocated to autograft (eight) or non-autograft (seven) groups. The autograft group were given an intradermal injection of a suspension of irradiated autologous tumour-cells mixed with intradermal BCG on the day of operation. Tests of cell-mediated immunity were repeated two weeks after operation. Five patients in each group received a course of radiotherapy to the mediastinum three weeks after operation. There was a rise in a cutaneous tuberculin reactivity (p=0.08) and total leucocyte count (p=0.09) in the autograft group postoperatively with a fall in total lymphocyte and T lymphocyte counts in the non-autograft group (p<0.05). These differences, however, were not followed by any difference in the frequency of tumour recurrence or the survival rate two years after operation. The results show that the immunological surveillance mechanism is impaired even in patients with early bronchial carcinoma and that it is possible to overcome postoperative immunological depression with specific immunotherapy combined with BCG. This treatment did not produce any clinical advantage in this small number of patients and the skin lesions caused the patients considerable discomfort. (author)

  2. Allergy, living and learning

    DEFF Research Database (Denmark)

    Chivato, T; Valovirta, E; Dahl, R;

    2012-01-01

    Allergy Living and Learning (ALL) is a European initiative designed to increase knowledge and understanding of people living with allergies in order to improve respiratory allergy care.......Allergy Living and Learning (ALL) is a European initiative designed to increase knowledge and understanding of people living with allergies in order to improve respiratory allergy care....

  3. Tuberculosis contact investigation with a new, specific blood test in a low-incidence population containing a high proportion of BCG-vaccinated persons

    Directory of Open Access Journals (Sweden)

    Meywald-Walter K

    2006-05-01

    Full Text Available Abstract Background BCG-vaccination can confound tuberculin skin test (TST reactions in the diagnosis of latent tuberculosis infection. Methods We compared the TST with a Mycobacterium tuberculosis specific whole blood interferon-gamma assay (QuantiFERON®-TB-Gold In Tube; QFT-G during ongoing investigations among close contacts of sputum smear positive source cases in Hamburg, Germany. Results During a 6-month period, 309 contacts (mean age 28.5 ± 10.5 years from a total of 15 source cases underwent both TST and QFT-G testing. Of those, 157 (50.8% had received BCG vaccination and 84 (27.2% had migrated to Germany from a total of 25 different high prevalence countries (i.e. >20 cases/100,000. For the TST, the positive response rate was 44.3% (137/309, whilst only 31 (10% showed a positive QFT-G result. The overall agreement between the TST and the QFT-G was low (κ = 0.2, with 95% CI 0.14.-0.23, and positive TST reactions were closely associated with prior BCG vaccination (OR 24.7; 95% CI 11.7–52.5. In contrast, there was good agreement between TST and QFT-G in non-vaccinated persons (κ = 0.58, with 95% CI 0.4–0.68, increasing to 0.68 (95% CI 0.46–0.81, if a 10-mm cut off for the TST was used instead of the standard 5 mm recommended in Germany. Conclusion The QFT-G assay was unaffected by BCG vaccination status, unlike the TST. In close contacts who were BCG-vaccinated, the QFT-G assay appeared to be a more specific indicator of latent tuberculosis infection than the TST, and similarly sensitive in unvaccinated contacts. In BCG-vaccinated close contacts, measurement of IFN-gamma responses of lymphocytes stimulated with M. tuberculosis-specific antigen should be recommended as a basis for the decision on whether to perform subsequent chest X-ray examinations or to start treatment for latent tuberculosis infection.

  4. Evaluation of the Immune Response to Interferon Gamma Release Assay and Tuberculin Skin Test Among BCG Vaccinated Children in East of Egypt: A Cross-Sectional Study.

    Science.gov (United States)

    Beshir, Mohamed Refaat; Zidan, Alaa Ebrahim; El-Saadny, Hosam Fathi; Ramadan, Raghdaa Abdelaziz; Karam, Nehad Ahmed; Amin, Ezzat Kamel; Mohamed, Marwa Zakaria; Abdelsamad, Nahla Mohamed

    2016-04-01

    Bacille Calmette-Guérin vaccine (BCG) vaccination is used routinely in most of countries, especially developing one. The efficacy of the BCG vaccination generally decreases with time. The tuberculin skin test (TST) is a most popular diagnostic test for suspicion of tuberculosis (TB) in children till now, but it has many false positives. The interferon-gamma release assay (IGRA) is more specific than TST for detection of childhood TB, as it is more specific to Mycobacterium tuberculosis.Evaluate the interferon gamma response and TST reaction in BCG vaccinated children in east of Egypt.150 children were included in the study aged 1 month to 12 years; the collected data from the children included, full history taking, clinical examination, examination for the presence or absence of BCG scar under direct light. All the children had performed TST, IGRA.TST was done for all studied group reveal 51.3% with size of reaction <5 mm, 39.3% with size of reaction = 5 to 9 mm while 9.3% with size of reaction ≥10 mm. Mean size of reaction was 4.07 mm. Interferon gamma release assay was done for all studied group reveal 5 children (3.3%) with positive test. There was significant difference between the size of TST reaction and age (P < 0.01) with old children were more frequent to show positive reaction. Also, children with age range 1 month to 1 year were frequently have negative IGRA test, while children with age range 4 years to 12 years were frequently have positive test (P < 0.01). There was moderate agreement between IGRA and TST results (Kappa [κ] = 0.475). With high agreement between IGRA and TST results in children with absent BCG scar (κ = 1000).Therefore, Interferon gamma release assays have higher specificity and lower cross-reactions with BCG vaccination and nontuberculous Mycobacteraie than TST. PMID:27124042

  5. Estimativa do risco de infecção tuberculosa em populações vacinadas pelo BCG Determining the risk of tuberculosis infection in BCG-vaccinated populations

    Directory of Open Access Journals (Sweden)

    Gilberto Ribeiro Arantes

    1992-04-01

    Full Text Available A revacinação de escolares com BCG, capaz de restaurar a alergia remanescente de vacinação realizada nos primeiros meses de vida, porém incapaz de modificar a alergia devida à infecção pelo M. tuberculosis, possibilitaria a quantificação da parcela dessa população infectada pelo bacilo de Koch. Foi desenvolvida pesquisa com o objetivo de avaliar a aplicabilidade desses pressupostos na estimativa do risco de infecção tuberculosa em áreas sob elevada cobertura com BCG. A população de estudo foi constituída por escolares com 6 a 9 anos de idade freqüentando escolas municipais da zona leste da cidade de São Paulo, durante o primeiro semestre letivo de 1988. De 11.455 vacinados, apenas 7.470 foram submetidos ao teste tuberculínico, revacinados em seguida e retestados dez semanas depois. Destes, 3.314 tinham sido vacinados no primeiro trimestre de vida com meia dose e os demais 4.156 receberam dose plena acima dessa idade (75% no primeiro ano de vida, 20% no segundo e 5% no terceiro. A contagem dos infectados, pelo confronto dos resultados pré e pós vacinais em tabelas de correlação, foi realizada segundo os critérios do método original e modificação introduzida pelos autores, separadamente para os vacinados no primeiro trimestre de vida e após essa idade. O risco de infecção foi, respectivamente, 0,35% e 0,37% com o critério original e 0,45% e 0,49% com o modificado. O referencial médio disponível para a área estudada, estimado por outros métodos, foi 0,55%. As diferenças entre critérios e idades e destes com o referencial não foram significantes (P > 0,05. Os resultados sugerem que o método é aplicável para a estimativa do risco de infecção tuberculosa na idade escolar, em vacinados com BCG no primeiro ano de vida, com dose plena de vacina.The revaccination of schoolchildren can restore the residual allergy induced by vaccination in the first years of life but can not modify the allergy resulting from a

  6. A Phase I study of an intravesically administered immunotoxin targeting EpCAM for the treatment of nonmuscle-invasive bladder cancer in BCG-refractory and BCG-intolerant patients

    Directory of Open Access Journals (Sweden)

    Mark Kowalski

    2010-11-01

    Full Text Available Mark Kowalski1, Joycelyn Entwistle2, Jeannick Cizeau2, Demi Niforos1, Shauna Loewen2, Wendy Chapman1, Glen C MacDonald21Viventia Biotechnologies Inc., Mississauga, ON, Canada; 2Viventia Biotechnologies Inc., Winnipeg, MB, CanadaPurpose: A Phase I dose-escalation study was performed to determine the maximum tolerated dose (MTD of the immunotoxin VB4-845 in patients with nonmuscle-invasive bladder cancer (NMIBC refractory to or intolerant of bacillus Calmette–Guerin (BCG. Secondary objectives included evaluation of the safety, tolerability, pharmacokinetics, immunogenicity, and efficacy of VB4-845.Patients and methods: Sixty-four patients with Grade 2 or 3, stage Ta or T1 transitional cell carcinoma or in situ carcinoma, either refractory to or intolerant of BCG therapy, were enrolled. Treatment was administered in ascending dose cohorts ranging from 0.1 to 30.16 mg. After receiving weekly instillations of VB4-845 to the bladder via catheter for 6 consecutive weeks, patients were followed for 4–6 weeks post-therapy and assessed at week 12.Results: An MTD was not determined, as a dose-limiting toxicity was not identified over the dose range tested. VB4-845 therapy was safe and well tolerated with most adverse events reported as mild; as a result, no patients were removed from the study in response to toxicity. By the end of the study, the majority of patients had developed antibodies to the exotoxin portion of VB4-845. A complete response was achieved in 39% of patients at the 12-week time point.Conclusions: VB4-845 dosed on a weekly basis for 6 weeks was very well tolerated at all dose levels. Although an MTD was not determined at the doses administered, VB4-845 showed evidence of an antitumor effect that warrants further clinical investigation for the treatment of NMIBC in this patient population.Keywords: Pseudomonas exotoxin A, anti-EpCAM, fusion protein, targeted therapy

  7. Virally Activated CD8 T Cells Home to Mycobacterium bovis BCG-Induced Granulomas but Enhance Antimycobacterial Protection Only in Immunodeficient Mice▿

    OpenAIRE

    Hogan, Laura H.; Co, Dominic O; Karman, Jozsef; Heninger, Erika; Suresh, M.; Sandor, Matyas

    2006-01-01

    The effect of secondary infections on CD4 T-cell-regulated chronic granulomatous inflammation is not well understood. Here, we have investigated the effect of an acute viral infection on the cellular composition and bacterial protection in Mycobacterium bovis strain bacille Calmette-Guérin (BCG)-induced granulomas using an immunocompetent and a partially immunodeficient murine model. Acute lymphocytic choriomeningitis virus (LCMV) coinfection of C57BL/6 mice led to substantial accumulation of...

  8. Influence of type of oil and surfactant concentration on the efficacy of emulsified Mycobacterium bovis BCG cell walls to induce tumor regression in guinea pigs.

    OpenAIRE

    Yarkoni, E; Rapp, H J

    1980-01-01

    The influence of mineral ol, squalane, squalene, hexadecane, or peanut oil and of the concentration of Tween 80 on the immunotherapeutic capability of emulsified Mycobacterium bovis Bacillus Calmette-Guérin (BCG) cell walls was studied in guinea pigs, each with an established dermal transplant of a syngeneic hepatocarcinoma and tumor cells in the draining lymph node. Immunotherapy consisted of an intratumoral injection of emulsified cell walls. Conditions were established under which therapeu...

  9. Enhanced superoxide release and tumoricidal activity by a postlavage, in situ pulmonary macrophage population in response to activation by Mycobacterium bovis BCG exposure.

    OpenAIRE

    Drath, D B

    1985-01-01

    The monocytic phagocyte population of rat lungs is heterogeneous. In addition to the freely lavagable alveolar macrophages, there is a fixed in situ tissue-associated subpopulation of pulmonary macrophages. The response of this subpopulation to classical macrophage activation by Mycobacterium bovis BCG exposure was monitored. Results indicate that this population can be activated both metabolically and functionally, as evidenced by enhanced release of superoxide anions and demonstrable tumori...

  10. malvolio, the Drosophila homologue of mouse NRAMP-1 (Bcg), is expressed in macrophages and in the nervous system and is required for normal taste behaviour.

    OpenAIRE

    V. RODRIGUES; Cheah, P. Y.; Ray, K; Chia, W.

    1995-01-01

    We report the sequence, expression pattern and mutant phenotype of malvolio (mvl), the Drosophila homologue of mammalian natural resistance-associated macrophage proteins (NRAMPs). In the mouse, this novel transporter is encoded by Bcg, a dominant gene that confers natural resistance to intracellular parasites. mvl was identified in a screen for mutants that affect taste behaviour. We show that loss-of-function as well as insertional mutants in mvl display defects in taste behaviour with no a...

  11. Proteome study of Francisella tularensis live vaccine strain-containing phagosome in Bcg/Nramp 1 congenic macrophages: Resistant allele contributes to permissive environment and susceptibility to infection

    Czech Academy of Sciences Publication Activity Database

    Kovářová, H.; Halada, Petr; Man, P.; Golovliov, I.; Kročová, Z.; Špaček, J.; Porkertová, S.; Nečasová, R.

    02, č. 2 (2002), s. 85-93. ISSN 1615-9853 R&D Projects: GA ČR GA310/99/1185 Keywords : innate immunity * phagosome * mass spectrometry Subject RIV: EE - Microbiology, Virology Impact factor: 4.007, year: 2002

  12. Proteome study of Francisella tularensis live vaccine strain-containing phagosome in Bcg/Nramp1 congenic macrophages: Resistant allele contributes to permissive environment and susceptibility to infection

    Czech Academy of Sciences Publication Activity Database

    Kovářová, Hana; Halada, Petr; Man, P.; Golovliov, I.; Špaček, J.; Porkertová, S.; Nečasová, R.

    č. 2 (2002), s. 85-93. ISSN 1615-9853 R&D Projects: GA ČR GA310/99/1185; GA MŠk LN00A033; GA AV ČR KSK5052113 Keywords : innate immunity * phagosome * francisella tularensis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.007, year: 2002

  13. Assisted Living Community Profile

    Science.gov (United States)

    ... for the Seniors Housing & Care Industry, reflects NCAL's philosophy of assisted living. 2 Data also from the ... Assisted Living Studies Clinical Practice Guidelines Health Information Technology In-Service Training Tools Periodicals State Regulatory Review ...

  14. Living with Spina Bifida

    Science.gov (United States)

    ... Us Information For... Media Policy Makers Living With Spina Bifida Language: English Español (Spanish) Recommend on Facebook Tweet ... of the website provides information about living with spina bifida at different ages. Spina bifida affects the entire ...

  15. Living with Atrial Fibrillation

    Science.gov (United States)

    ... Topics » Atrial Fibrillation » Living With Atrial Fibrillation Explore Atrial Fibrillation What Is... Types Other Names Causes Who Is at Risk Signs & Symptoms Diagnosis Treatments Prevention Living With Clinical Trials Links Related Topics Arrhythmia ...

  16. Constraining the Scatter in the Mass-Richness Relation of maxBCG Clusters With Weak Lensing and X-ray Data

    Energy Technology Data Exchange (ETDEWEB)

    Rozo, Eduardo; /Ohio State U.; Rykoff, Eli S.; /UC, Santa Barbara; Evrard, August; /Michigan U.; Becker, Matthew R.; /Chicago U.; McKay, Timothy; /Michigan U.; Wechsler, Risa H.; /SLAC; Koester, Benjamin P.; /Chicago U. /KICP, Chicago; Hao, Jiangang; /Michigan U.; Hansen, Sarah; /Chicago U. /KICP, Chicago; Sheldon, Erin; /New York U.; Johnston, David; /Houston U.; Annis, James T.; /Fermilab; Frieman, Joshua A.; /Chicago U. /KICP, Chicago /Fermilab

    2009-08-03

    We measure the logarithmic scatter in mass at fixed richness for clusters in the maxBCG cluster catalog, an optically selected cluster sample drawn from SDSS imaging data. Our measurement is achieved by demanding consistency between available weak lensing and X-ray measurements of the maxBCG clusters, and the X-ray luminosity-mass relation inferred from the 400d X-ray cluster survey, a flux limited X-ray cluster survey. We find {sigma}{sub lnM|N{sub 200}} = 0.45{sub -0.18}{sup +0.20} (95%CL) at N{sub 200} {approx} 40, where N{sub 200} is the number of red sequence galaxies in a cluster. As a byproduct of our analysis, we also obtain a constraint on the correlation coefficient between lnL{sub X} and lnM at fixed richness, which is best expressed as a lower limit, r{sub L,M|N} {ge} 0.85 (95% CL). This is the first observational constraint placed on a correlation coefficient involving two different cluster mass tracers. We use our results to produce a state of the art estimate of the halo mass function at z = 0.23 - the median redshift of the maxBCG cluster sample - and find that it is consistent with the WMAP5 cosmology. Both the mass function data and its covariance matrix are presented.

  17. Impact of the BCG vaccination policy on tuberculous meningitis in children under 6 years in metropolitan France between 2000 and 2011.

    Science.gov (United States)

    Van Bui, T; Lévy-Bruhl, D; Che, D; Antoine, D; Jarlier, V; Robert, J

    2015-01-01

    In France, Bacillus Calmette–Guérin (BCG) vaccination by multipuncture device was withdrawn in 2006. In 2007, universal mandatory BCG vaccination was replaced by vaccination of high-risk children. To evaluate the impact of these changes on tuberculous meningitis (TBM) epidemiology, data on culture-positive and culture-negative (or unknown microbiological result) TBM in ≤5 years olds were collected from 2000–2011. Ten culture-positive and 17 culture-negative TBM cases were identified, with an annual incidence rate ranging from 0.16 to 0.66 cases per 10 million inhabitants. The average annual numbers of TBM cases were 2.7 and 1.8 from 2000–2005 and 2006–2011, respectively. In Ile-de-France where all children are considered at risk, the overall incidence rates were 1.14 and 0.29 per million for the two periods. In other regions where only at-risk children are vaccinated since 2007, rates were 0.30 and 0.47, respectively. None of these differences were significant. Annual incidence rates for each one year age group cohort were comparable before and after changes. Childhood TBM remains rare in France. No increase in incidence was observed after changes in BCG vaccination strategy. Ongoing surveillance should be maintained, as a slight increase in TBM in the coming years remains possible, in the context of suboptimal vaccination coverage of high-risk children. PMID:25811645

  18. CONSTRAINING THE SCATTER IN THE MASS-RICHNESS RELATION OF maxBCG CLUSTERS WITH WEAK LENSING AND X-RAY DATA

    International Nuclear Information System (INIS)

    We measure the logarithmic scatter in mass at fixed richness for clusters in the maxBCG cluster catalog, an optically selected cluster sample drawn from Sloan Digital Sky Survey imaging data. Our measurement is achieved by demanding consistency between available weak-lensing and X-ray measurements of the maxBCG clusters, and the X-ray luminosity-mass relation inferred from the 400 days X-ray cluster survey, a flux-limited X-ray cluster survey. We find σlnM|N200=0.45-0.18+0.20 (95% CL) at N 200 ∼ 40, where N 200 is the number of red sequence galaxies in a cluster. As a byproduct of our analysis, we also obtain a constraint on the correlation coefficient between ln LX and ln M at fixed richness, which is best expressed as a lower limit, r L,M|N ≥ 0.85(95% CL). This is the first observational constraint placed on a correlation coefficient involving two different cluster mass tracers. We use our results to produce a state-of-the-art estimate of the halo mass function at z = 0.23-the median redshift of the maxBCG cluster sample-and find that it is consistent with the WMAP5 cosmology. Both the mass function data and its covariance matrix are presented.

  19. Boosting BCG-primed mice with chimeric DNA vaccine HG856A induces potent multifunctional T cell responses and enhanced protection against Mycobacterium tuberculosis.

    Science.gov (United States)

    Ji, Ping; Hu, Zhi-Dong; Kang, Han; Yuan, Qin; Ma, Hui; Wen, Han-Li; Wu, Juan; Li, Zhong-Ming; Lowrie, Douglas B; Fan, Xiao-Yong

    2016-02-01

    The tuberculosis pandemic continues to rampage despite widespread use of the current Bacillus Calmette-Guerin (BCG) vaccine. Because DNA vaccines can elicit effective antigen-specific immune responses, including potent T cell-mediated immunity, they are promising vehicles for antigen delivery. In a prime-boost approach, they can supplement the inadequate anti-TB immunological memory induced by BCG. Based on this, a chimeric DNA vaccine HG856A encoding Mycobacterium tuberculosis (M. tuberculosis) immunodominant antigen Ag85A plus two copies of ESAT-6 was constructed. Potent humoral immune responses, as well as therapeutic effects induced by this DNA vaccine, were observed previously in M. tuberculosis-infected mice. In this study, we further evaluated the antigen-specific T cell immune responses and showed that repeated immunization with HG856A gave modest protection against M. tuberculosis challenge infection and significantly boosted the immune protection primed by BCG vaccination. Enhanced protection was accompanied by increased multifunctional Th1 CD4(+) T cell responses, most notably by an elevated frequency of M. tuberculosis antigen-specific IL-2-producing CD4(+) T cells post-vaccination. These data confirm the potential of chimeric DNA vaccine HG856A as an anti-TB vaccine candidate. PMID:26111521

  20. Living Planet Report 2004

    OpenAIRE

    Loh, J; Wackernagel, M.

    2004-01-01

    The Living Planet Report is WWF's periodic update on the state of the world's ecosystems. This is measured using 2 main indicators. The first indicator is the fact that the Living Planet Index is derived from trends over the past 30 years in populations of hundreds of species of birds, mammals, reptiles, amphibians and fish. The Living Planet Index (LPI) is an indicator of the state of the world's biodiversity: it measures trends in populations of vertebrate species living in terrestrial, fre...

  1. I Live with Psoriasis

    Science.gov (United States)

    ... version of this page please turn Javascript on. Feature: Living with Psoriasis I Live with Psoriasis Past Issues / Fall 2013 Table of ... courtesy of Stephen Voss/ National Psoriasis Foundation "I live with the disease," she says, cautious about being treated with narrow band ultraviolet light (UVB) for ...

  2. Biometric Fingerprint Liveness Detection

    OpenAIRE

    Váňa, T.

    2015-01-01

    This paper deals with biometric fingerprint liveness detection. A software-based liveness detection approach using neural network is proposed. To distinguish between live and fake samples, three image quality features extracted from one image are used. The algorithm is tested on LivDet database comprising real and fake images acquired with three sensors.

  3. "N0ticing"in second language acquisition

    Institute of Scientific and Technical Information of China (English)

    邵燕

    2010-01-01

    Learners should"notice"something when they Learn English.If they can absorb some English knowledge through "noticing",it must be easier for English learners to become input into intake.From above,there are several factors that influence "noticing"in the process where input is changed into intake.When we learn English,we also should pay more attention to these factors,for they will help us how to notice more in learning English and how to improve our English easily.

  4. Efficacy of intramuscular BCG polysaccharide nucleotide on mild to moderate bronchial asthma accompanied with allergic rhinitis: a randomized, double blind, placebo-controlled study

    Institute of Scientific and Technical Information of China (English)

    LI Jing; LUO Ding-fen; LI Sui-ying; SUN Bao-qing; ZHONG Nan-shan

    2005-01-01

    Background Atopy is a state of allergy to common antigens and is founded on an immune disturbance of exuberant Th2 activity and IgE production. There is also epidemiological and experimental evidence that exposure to mycobacteria has the potential to suppress the development of asthma or atopy. Since Th1 and Th2 immune mechanisms are significantly antagonistic, it is hypothesized that mycobacterial exposure may moderate atopic disease by modification of immune responses. Methods One hundred and twenty mild to moderate persistent asthmatics accompanied with allergic rhinitis were randomly divided into four groups with one injection every other day for 18 times for group A with 1 ml of normal saline, B with 0.5 mg of Bacillus Calmette-Guérin polysaccharide nucleotide (BCG-PSN) and C with 1 mg of BCG-PSN, 36 times for group D with 0.5 mg of BCG-PSN. Markers for the severity of asthma and rhinitis including the amount of inhaled corticosteriod, bronchodilator and oral H1 blocker-loratidine being used to obtain optimal symptomatic control, symptom scores of asthma and allergic rhinitis, peak expiratory flow (PEF), histamine provocative dose that produces at least a 20% change in forced expiratory volume with in 1 second (PD20-FEV1), blood IgE levels as well as dermatophagoides pteronysinus (DP) and dermatophagoides farinae (DF) skin prick test were measured every visit for 6 months. Results There were no differences for symptom scores of asthma, daily use of bronchodilator, PEF, PD20-FEV1, blood IgE as well as DF and DP skin prick test among the four groups. Score for allergic rhinitis decreased significantly in groups B, C and D on day 36 and 72 as compared with group A (P<0.05). Score for allergic rhinitis increased after day 72 in group B and C while it was significantly lower in group D (P<0.05). The patients in group D used less amount of inhaled beclomethosone than other groups (P<0.05) from day 72 after the treatment to day 180. Oral loratadine consumption in

  5. Characterization of immune response to killed leishmania major promastigotes plus BCG vaccine in Sudanese volunteers: a double-blind placebo controlled study

    International Nuclear Information System (INIS)

    This work was examined whether intradermal immunization of healthy adult Sudanese volunteers with killed leishmania major (KLM) promastigotes plus BCG would induce antigen-specific T cell responses. Only healthy Sudanese volunteers with negative reactivity to leishmania skin test and with ≤20 mm induration of reactivity to purified protein derivative (PPD) were included in the trial. Group (A) (n=3): received a single dose (0.1ml) at a concentration of 10 mg protein of a whole cell component of KLM promastigotes/ml BCG, group (B) (n=12): received as a single dose of viable attenuated BCG alone (0.1 ml) at a concentration of 1 mg protein/ml diluent, group (C) (n=11): received the vaccine diluent only (Placebo) (o.1 ml). Study subjects were tested for their immunological and clinical responses before intervention, . Following vaccination 65% of group (A) subjects converted in their reactivity to leishmanin skin testing,non of the BCG vaccinated subjects converted in leishmanin skin test and only one subject of group (C) became leishmanin positive. Levels of Interferon-gamma (IFN-γ), interleukin-5 (IL-5) and interleukin-10 (IL-10) were measured by a double sandwich enzyme-linked immunosorbent assay (ELISA). A vaccine was considered as a positive responder in terms of cytokine production when the level of the produced cytokine was equal to the 80th percentile of the levels produced by the volunteers in the placebo group. 92% of the group vaccinated with KLM=BCG had circulating T cells. No significant of IL-5 or Il-10 was reported in any of the volunteers in the three group. Levels of antileishmania specific IgG were measured by ELISA in optical densities. Volunteers with mean antibody titre above the cut-off point (mean=3X standard deviation) were considered to have positive scores. Accordingly after vaccination 7.69% one volunteers in group (A) had a positive antibody response corresponding to 0% in the other two groups. No serious side effects were reported

  6. Assessment of different formulations of oral Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine in rodent models for immunogenicity and protection against aerosol challenge with M. bovis.

    Science.gov (United States)

    Clark, Simon; Cross, Martin L; Smith, Alan; Court, Pinar; Vipond, Julia; Nadian, Allan; Hewinson, R Glyn; Batchelor, Hannah K; Perrie, Yvonne; Williams, Ann; Aldwell, Frank E; Chambers, Mark A

    2008-10-29

    Bovine tuberculosis (bTB) caused by infection with Mycobacterium bovis is causing considerable economic loss to farmers and Government in the United Kingdom as its incidence is increasing. Efforts to control bTB in the UK are hampered by the infection in Eurasian badgers (Meles meles) that represent a wildlife reservoir and source of recurrent M. bovis exposure to cattle. Vaccination of badgers with the human TB vaccine, M. bovis Bacille Calmette-Guérin (BCG), in oral bait represents a possible disease control tool and holds the best prospect for reaching badger populations over a wide geographical area. Using mouse and guinea pig models, we evaluated the immunogenicity and protective efficacy, respectively, of candidate badger oral vaccines based on formulation of BCG in lipid matrix, alginate beads, or a novel microcapsular hybrid of both lipid and alginate. Two different oral doses of BCG were evaluated in each formulation for their protective efficacy in guinea pigs, while a single dose was evaluated in mice. In mice, significant immune responses (based on lymphocyte proliferation and expression of IFN-gamma) were only seen with the lipid matrix and the lipid in alginate microcapsular formulation, corresponding to the isolation of viable BCG from alimentary tract lymph nodes. In guinea pigs, only BCG formulated in lipid matrix conferred protection to the spleen and lungs following aerosol route challenge with M. bovis. Protection was seen with delivery doses in the range 10(6)-10(7) CFU, although this was more consistent in the spleen at the higher dose. No protection in terms of organ CFU was seen with BCG administered in alginate beads or in lipid in alginate microcapsules, although 10(7) in the latter formulation conferred protection in terms of increasing body weight after challenge and a smaller lung to body weight ratio at necropsy. These results highlight the potential for lipid, rather than alginate, -based vaccine formulations as suitable delivery

  7. A derivation of masses and total luminosities of galaxy groups and clusters in the maxBCG catalogue

    CERN Document Server

    Proctor, Robert N; Azanha, Luiz; Dupke, Renato; Overzier, Roderik

    2015-01-01

    We report the results of a multi-waveband analysis of the masses and luminosities of $\\sim$600 galaxy groups and clusters identified in the maxBCG catalogue. These data are intended to form the basis of future work on the formation of the "$m_{12}$ gap" in galaxy groups and clusters. We use SDSS spectroscopy and $g$, $r$ and $i$ band photometry to estimate galaxy group/cluster virial radii, masses and total luminosities. In order to establish the robustness of our results, we compare them with literature studies that utilize a variety of mass determinations techniques (dynamical, X-ray, weak lensing) and total luminosities estimated in the $B$, $r$, $i$, and $K$ wavebands. We also compare our results to predictions derived from the Millennium Simulation. We find that, once selection effects are properly accounted for, excellent agreement exists between our results and the literature with the exception of a single observational study. We also find that the Millennium Simulation does an excellent job of predict...

  8. Low in vitro response to PPD and PHA in lymphocytes from BCG-induced pleurisy in guinea pigs

    International Nuclear Information System (INIS)

    In order to study any correlation between functional properties of lymphocytes in BCG-induced pleural exudation and the development of the pleurisy a previously described experimental model was used. This model with a duration of effusion of more than 17 days has characteristic stages. From the third day and onwards there are lymphocytes in sufficient amount for in vitro cultures. Proliferation of lymphocytes from the fluid was measured as uptake of 14C-thymidine. The response of the lymphocytes to PPD tuberculin and to phytohemagglutinin (PHA) was studied, and their spontaneous activity was measured. Comparisons were made with lymphocytes from regional lymph nodes. Pleural lymphocytes sampled on the third post-induction day did not respond to PPD or PHA stimulation. In later stages, pleural lymphocytes were stimulated by PPD to approximately the same degree as the lymph node lymphocytes. The response to PHA was weak at all stages of pleurisy, though in later stages there were some cases with high values. Variations in activation ability, related to disease staging, were demonstrated. However, low activities, and variability of the responces, without concomitant variations in disease, speak against a connection between the course of disease and functional status of the lymphocytes as measured in this study. (authors)

  9. Modification of in vitro and in vivo BCG cell wall-induced immunosuppression by treatment with chemotherapeutic agents or indomethacin

    International Nuclear Information System (INIS)

    The in vitro inhibition of spleen cell blastogenesis response and the in vivo enhancement of tumor growth are phenomena associated with BCG cell wall (BCGcw) immunization. What effect treatment with chemotherapeutic agents and the prostaglandin inhibitor indomethacin would have on the in vitro and in vivo responses to BCGcw immunization was evaluated. In vitro blastogenesis studies showed that chemotherapy pretreatment prior to immunization with BCGcw resulted in a restoration of the spleen cell blastogenesis response. In blastogenesis addback studies, where BCGcw-induced irradiated splenic suppressor cells were admixed with normal cells, less inhibition of blastogenesis occurred when spleen cells were obtained from rats that had received the combined treatment of chemotherapy and BCGcw immunization versus only BCGcw immunization. The cocultivation of spleen cells from BCGcw-immunized rats with indomethacin resulted in a 30-40% restoration of the blastogenesis response. In vivo studies showed that BCGcw-mediated enhancement of intramuscular tumor growth of the 3924a ACI rat tumor could be abrogated by either pretreatment with busulfan or mitomycin or by the feeding of indomethacin

  10. Writing lives in sport

    DEFF Research Database (Denmark)

    Christensen, Mette Krogh

    Writing lives in sport is a book of stories about sports-persons. The people concerned include sports stars, sports people who are not quite so famous, and relatively unknown physical education teachers and sports scientists.Writing lives in sport raises questions about writing biographies...... in the academis world of sport studies. It does not set out to be a methodological treatise but through the writing of lives in sports does raise questions of method. Each essay in this collection deals with problems of writing sports-people's lives. These essays could be said to fall along a spectrum from those...

  11. [Support in living].

    Science.gov (United States)

    Krebs, H

    1993-06-01

    "Lebenshilfe" (help in living) is of crucial importance for the organization of live of persons with a handicap. This help in living, training and social integration, however, requires an image of the handicapped person that unrestrictedly recognizes her right to live and to be a human being with a handicap. But todays hedonistic and preference-utilitarian social trends make other, selecting value judgements. This article comments on these dubious ethical positions critically and develops a paradigmatic, positive point of view. This statement is partly based on the principles of 2 self-help organizations of the same name ("Lebenshilfe für geistig Behinderte") in Germany and in Austria. PMID:8374501

  12. Asociación entre tuberculosis infantil grave e inmunización previa con BCG en un hospital de referencia nacional, Perú 1990-2000 Association between severe tuberculosis in children and previous BCG immunization in a national referral Hospital, Peru 1990-2000

    OpenAIRE

    Félix Llanos-Tejada; Hernán del Castillo

    2012-01-01

    El objetivo del estudio fue determinar la asociación entre la inmunización con BCG y tuberculosis grave (TB). Se realizó un estudio retrospectivo, se incluyó fichas de pacientes atendidos en el servicio de neumología del Instituto Nacional de Salud del Niño de Perú, entre los años 1990-2000. Se revisaron un total de 2106 casos de TB entre los que había 259 casos graves (TB miliar o meningoencefalitis por TB). Del total, 497 casos no tenían antecedente de inmunización con BCG; 202 tenían TB gr...

  13. Animals that Live Longest

    Institute of Scientific and Technical Information of China (English)

    饶扬志

    2000-01-01

    Reptiles(爬行类) are animals that live longest. The turtle's(海龟)long life is legendary(传奇的), no one has ever been able to calculate the exact age of the turtle, and for good reason, tortoises live a lot longer than humans do.

  14. Interventions in everyday lives

    DEFF Research Database (Denmark)

    Dreier, Ole

    2015-01-01

    The purpose of psychotherapy is to help clients address and overcome problems troubling them in their everyday lives. Therapy can therefore only work if clients include it in their ongoing lives to deal with their problems. Detailed, systematic research is needed on how clients do so in their...

  15. Is It Living?

    Science.gov (United States)

    Keeley, Page

    2011-01-01

    The word "living" is commonly used throughout elementary science lessons that focus on the biological world. It is a word teachers often take for granted when teaching life science concepts. How similar the constructed meaning of a common word like "living" is to the meaning intended by the teacher or instructional materials depends on how a…

  16. Living the Utopia

    DEFF Research Database (Denmark)

    Davis, John; Warring, Anette Elisabeth

    2011-01-01

    This article examines experiments in communal living in Britain and Denmark in the early 1970s, using life-story interviews from seventeen members of two British and two Danish communes. It examines communal living as a fusion of radical political principles with the practice of experimental coll...

  17. Living with Worms

    DEFF Research Database (Denmark)

    Bertoni, Filippo

    2016-01-01

    The thesis explores what living together can offer in rethinking political theory and in creating a space in which "politics" is not just a matter between people, but also with nature. These lessons about living together emerge from fieldwork around practices in which worms are central. Thus, the...

  18. Live and Dead Nodes

    DEFF Research Database (Denmark)

    Jørgensen, Sune Lehman; Jackson, A. D.

    2005-01-01

    In this paper, we explore the consequences of a distinction between `live' and `dead' network nodes; `live' nodes are able to acquire new links whereas `dead' nodes are static. We develop an analytically soluble growing network model incorporating this distinction and show that it can provide a q...

  19. Evaluating Living Standard Indicators

    Directory of Open Access Journals (Sweden)

    Birčiaková Naďa

    2015-09-01

    Full Text Available This paper deals with the evaluation of selected available indicators of living standards, divided into three groups, namely economic, environmental, and social. We have selected six countries of the European Union for analysis: Bulgaria, the Czech Republic, Hungary, Luxembourg, France, and Great Britain. The aim of this paper is to evaluate indicators measuring living standards and suggest the most important factors which should be included in the final measurement. We have tried to determine what factors influence each indicator and what factors affect living standards. We have chosen regression analysis as our main method. From the study of factors, we can deduce their impact on living standards, and thus the value of indicators of living standards. Indicators with a high degree of reliability include the following factors: size and density of population, health care and spending on education. Emissions of carbon dioxide in the atmosphere also have a certain lower degree of reliability.

  20. Lipid-formulated bcg as an oral-bait vaccine for tuberculosis: vaccine stability, efficacy, and palatability to brushtail possums (Trichosurus vulpecula) in New Zealand.

    Science.gov (United States)

    Cross, Martin L; Henderson, Ray J; Lambeth, Matthew R; Buddle, Bryce M; Aldwell, Frank E

    2009-07-01

    Bovine tuberculosis (Tb), due to infection with virulent Mycobacterium bovis, represents a threat to New Zealand agriculture due to vectorial transmission from wildlife reservoir species, principally the introduced Australian brushtail possum (Trichosurus vulpecula). An oral-delivery wildlife vaccine has been developed to immunize possums against Tb, based on formulation of the human Tb vaccine (M. bovis BCG) in edible lipid matrices. Here BCG bacilli were shown to be stable in lipid matrix formulation for over 8 mo in freezer storage, for 7 wk under room temperature conditions, and for 3-5 wk under field conditions in a forest/pasture margin habitat (when maintained in weatherproof bait-delivery sachets). Samples of the lipid matrix were flavored and offered to captive possums in a bait-preference study: a combination of 10% chocolate powder with anise oil was identified as the most effective attractant/palatability combination. In a replicated field study, 85-100% of wild possums were shown to access chocolate-flavored lipid pellets, when baits were applied to areas holding approximately 600-800 possums/km(2). Finally, in a controlled vaccination/challenge study, chocolate-flavored lipid vaccine samples containing 10(8) BCG bacilli were fed to captive possums, which were subsequently challenged via aerosol exposure to virulent M. bovis: vaccine immunogenicity was confirmed, and protection was identified by significantly reduced postchallenge weight loss in vaccinated animals compared to nonvaccinated controls. These studies indicate that, appropriately flavored, lipid delivery matrices may form effective bait vaccines for the control of Tb in wildlife. PMID:19617486